Bilateral electrical stimulation therapy for bladder dysfunction

ABSTRACT

A medical device is configured to deliver a first stimulation therapy to a patient, and, upon detecting a trigger event, deliver a second stimulation therapy to the patient. In some examples, the first stimulation therapy includes bilateral stimulation in which stimulation is delivered at different times to two lateral sides of the patient and the second stimulation therapy includes substantially simultaneous bilateral stimulation therapy to two lateral sides of the patient. In some examples, the second stimulation therapy may elicit a stronger inhibitory physiological response related to incontinence (e.g., inhibition of bladder contractions) than the first stimulation therapy. The trigger event may include, for example, any one or more of detection of a physiological condition indicative of an increased possibility of an involuntary voiding event or an imminent involuntary voiding event, input from the patient, a predetermined time of day, or expiration of a timer.

This application claims the benefit of U.S. Provisional Application Ser.No. 61/437,081 by Su et al., which was filed on Jan. 28, 2011, and isentitled “BILATERAL ELECTRICAL STIMULATION THERAPY FOR BLADDERDYSFUNCTION.” U.S. Provisional Application Ser. No. 61/437,081 by Su etal. is incorporated herein by reference in its entirety

TECHNICAL FIELD

The disclosure relates to electrical stimulation therapy, and, moreparticularly, stimulation therapy for the management of bladderdysfunction.

BACKGROUND

Bladder dysfunction, such as an overactive bladder, urgency, or urinaryincontinence, is a problem that may afflict people of all ages, genders,and races. Various muscles, nerves, organs and conduits within thepelvic floor cooperate to collect, store and release urine. A variety ofdisorders may compromise urinary tract performance, and contribute to anoveractive bladder, urgency, or urinary incontinence. Many of thedisorders may be associated with aging, injury or illness.

Urinary incontinence may include urge incontinence and stressincontinence. In some examples, urge incontinence may be caused bydisorders of peripheral or central nervous systems that control bladdermicturition reflexes. Some patients may also suffer from nerve disordersthat prevent proper triggering and operation of the bladder, sphinctermuscles or nerve disorders that lead to overactive bladder activities orurge incontinence.

In some cases, urinary incontinence can be attributed to impropersphincter function, either in the internal urinary sphincter or externalurinary sphincter. Nerves running though the pelvic floor stimulatecontractility in the sphincter. An improper communication between thenervous system and the urethra or urinary sphincter can result in abladder dysfunction, such as overactive bladder, urgency, urgeincontinence, urine retention disorder, or another type of urinaryincontinence.

SUMMARY

In general, the disclosure is directed to managing a bladder dysfunctionby delivering a first stimulation therapy to a patient, and, upondetecting a trigger event, delivering a second stimulation therapy tothe patient. The first stimulation therapy includes bilateralstimulation in which stimulation is delivered at different times to twolateral sides of the patient. For example, a stimulation period duringwhich stimulation is delivered to a first lateral side of the patientmay not overlap with a stimulation period during which stimulation isdelivered to a second lateral side of the patient. In some examples, theelectrical stimulation signal trains (e.g., pulse trains) that elicit atherapeutic effect from the patient may be delivered to one lateral sideof the patient at a time, such that the signal trains do not overlapduring the first stimulation therapy. The second stimulation therapyincludes substantially simultaneous bilateral stimulation therapy to thetwo lateral sides of the patient. For example, the electricalstimulation signal trains may be delivered to both lateral sides of thepatient at the same time, such that the stimulation trains overlap. Thesecond stimulation therapy may be selected to elicit a strongerinhibitory physiological response related to incontinence (e.g.,inhibition of bladder contractions) than the first stimulation therapy.

In one aspect, the disclosure is directed to a method that comprises,with a processor, controlling a stimulation generator to deliver a firstelectrical stimulation therapy to a patient, wherein the firstelectrical stimulation therapy comprises delivery of electricalstimulation to a first lateral side of the patient and a second lateralside of the patient at different times, after initiating delivery of thefirst electrical stimulation therapy, detecting a trigger event, and, inresponse to detecting the trigger event, with the processor, controllingthe stimulation generator to deliver a second electrical stimulationtherapy to the patient, wherein the second electrical stimulationtherapy comprises delivery of electrical stimulation substantiallysimultaneously to the first and second lateral sides of the patient.

In another aspect, the disclosure is directed to a system comprising astimulation generator configured to generate and deliver electricalstimulation to a patient, and a processor configured to control thestimulation generator to deliver a first electrical stimulation therapyto the patient, detect a trigger event after initiating delivery of thefirst electrical stimulation therapy and, in response to detecting thetrigger event, control the stimulation generator to deliver a secondelectrical stimulation therapy to the patient. The first electricalstimulation therapy comprises delivery of electrical stimulation to afirst lateral side of the patient and a second lateral side of thepatient at different times. The second electrical stimulation therapycomprises delivery of electrical stimulation substantiallysimultaneously to the first and second lateral sides of the patient.

In a further aspect, the disclosure is directed to a system thatcomprises means for delivering electrical stimulation therapy to apatient, means for detecting a trigger event after initiating deliveryof the first electrical stimulation therapy, and means for controllingthe means for delivering electrical stimulation therapy. The means forcontrolling is configured to control the means for delivering electricalstimulation therapy to deliver a first electrical stimulation therapy toa patient, where the first electrical stimulation therapy comprisesdelivery of electrical stimulation to a first lateral side of thepatient and a second lateral side of the patient at different times. Themeans for controlling is further configured to, in response to detectionof the trigger event, control the means for delivering electricalstimulation therapy to deliver a second electrical stimulation therapyto the patient, wherein the second electrical stimulation therapycomprises delivery of electrical stimulation substantiallysimultaneously to the first and second lateral sides of the patient.

In an additional aspect, the disclosure is directed to acomputer-readable storage medium comprising instructions that, whenexecuted by a processor, cause the processor to control a stimulationgenerator to deliver a first electrical stimulation therapy to apatient, wherein the first electrical stimulation therapy comprisesdelivery of electrical stimulation to a first lateral side of thepatient and a second lateral side of the patient at different times,detect a trigger event after the first stimulation therapy is initiated,and control the stimulation generator to deliver a second electricalstimulation therapy to the patient in response to detecting the triggerevent. The second electrical stimulation therapy comprises delivery ofelectrical stimulation substantially simultaneously to the first andsecond lateral sides of the patient.

In another aspect, the disclosure is directed to a computer-readablestorage medium, which may be an article of manufacture. Thecomputer-readable storage medium includes computer-readable instructionsfor execution by a processor. The instructions cause a programmableprocessor to perform any part of the techniques described herein. Theinstructions may be, for example, software instructions, such as thoseused to define a software or computer program. The computer-readablemedium may be a computer-readable storage medium such as a storagedevice (e.g., a disk drive, or an optical drive), memory (e.g., a Flashmemory, read only memory (ROM), or random access memory (RAM)) or anyother type of volatile or non-volatile memory that stores instructions(e.g., in the form of a computer program or other executable) to cause aprogrammable processor to perform the techniques described herein. Insome examples, the computer-readable storage medium may benon-transitory.

The details of one or more example are set forth in the accompanyingdrawings and the description below. Other features, objects, andadvantages will be apparent from the description and drawings, and fromthe claims.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 is a conceptual diagram of an example therapy system thatdelivers a first stimulation therapy to a patient and, when triggered, asecond stimulation therapy that includes substantially simultaneousbilateral stimulation.

FIG. 2 illustrates a conceptual anatomical view of portions of a pelvicfloor of a female patient, and an implanted therapy system that isconfigured to deliver bilateral stimulation to tissue sites proximate atleast one nerve of the pelvic floor.

FIG. 3 is a block diagram illustrating an example configuration of animplantable medical device (IMD), which may be utilized in the systemsshown in FIGS. 1 and 2.

FIG. 4 is a block diagram illustrating an example configuration of anexternal programmer which may be utilized in the systems shown in FIGS.1 and 2.

FIG. 5 is a flow diagram that illustrates an example technique fordelivering stimulation therapy to a patient, where the therapy includesa first stimulation therapy and a second stimulation therapy.

FIG. 6 is a flow diagram of another example technique for deliveringfirst and second stimulation therapies to a patient.

FIG. 7 is a flow diagram of another example technique for deliveringfirst and second stimulation therapies to a patient, which includesdelivering the second stimulation therapy until a voluntary voidingevent of the patient is detected.

FIG. 8 is a flow diagram that illustrates an example technique fordelivering a first stimulation therapy in a closed loop manner.

FIGS. 9A-9C are schematic illustrations of example stimulation signalsdelivered to the first and second sides of a patient during the firstelectrical stimulation therapy.

FIGS. 10A-10F are schematic illustrations of example stimulation signalsdelivered to the first and second sides of a patient during the secondelectrical stimulation therapy.

FIGS. 11-13 are graphs that illustrate examples of changes in bladdercontraction frequency of test subjects in response to unilateralstimulation, bilateral stimulation delivered at different times to twolateral sides of the subjects, and substantially simultaneous bilateralstimulation.

FIGS. 14A and 14B are additional graphs that illustrate examples ofchanges in bladder contraction frequency of test subjects in response tounilateral stimulation, bilateral stimulation delivered at differenttimes to two lateral sides of the subjects, and substantiallysimultaneous bilateral stimulation.

FIGS. 15A and 15B are graphs that illustrate the effect of pulse matchand pulse mismatch on bladder contraction frequency during delivery of,substantially simultaneous bilateral stimulation.

FIG. 16 is a conceptual diagram of a therapy system that is configuredto determine an impedance of a bladder of a patient.

DETAILED DESCRIPTION

Bladder dysfunction refers to a condition of improper functioning of thebladder or urinary tract, and may include, for example, an overactivebladder, urgency, urine retention disorder, or urinary incontinence.Urgency is a sudden, compelling urge to urinate, and may often, thoughnot always, be associated with urinary incontinence. Urinaryincontinence refers to a condition of involuntary voiding events (i.e.,involuntary loss of urine in the case of urinary incontinence), and mayinclude urge incontinence, stress incontinence, or both stress and urgeincontinence, which may be referred to as mixed urinary incontinence. Asused in this disclosure, the term “urinary incontinence” includesdisorders in which urination occurs when not desired, such as stress orurge incontinence.

One type of therapy that has been proposed for managing bladderdysfunction (e.g., minimizing bladder contractions and/or the number ofinvoluntary voiding events) includes delivery of electrical stimulationto a target tissue site within a patient. For example, delivery ofelectrical stimulation from an implantable medical device to a targettissue site proximate any one or more of a spinal nerve, a sacral nerve,a pudendal nerve, dorsal genital nerve, a tibial nerve, an inferiorrectal nerve, a perineal nerve, or branches of any of the aforementionednerves to modulate the nerve activities may provide an effective therapyfor managing bladder dysfunction. As an example, electrical stimulationto modulate the activity of the sacral and/or pudendal nerve (orbranches thereof) may help reduce bladder contraction frequency, whichcan mitigate urgency.

FIG. 1 is a conceptual diagram that illustrates an example of a therapysystem 10 that delivers electrical stimulation therapy to patient 12 tomanage a bladder dysfunction of patient 12. As described in furtherdetail below, in some examples, therapy system 10 delivers a firstelectrical stimulation therapy, and, when triggered, a second electricalstimulation therapy to manage a bladder dysfunction of patient 12.Therapy system 10 includes an implantable medical device (IMD) 14, whichis coupled to leads 16, 18. System 10 also includes an externalprogrammer 20, which communicates with IMD 14 via a wirelesscommunication protocol, and sensor 22, which generates a signalindicative of a physiological parameter of patient 12. The physiologicalparameter is indicative of a condition of patient 12 related to bladderdysfunction, e.g., relating to a bladder fill level, bladder contractionor a posture or activity level of patient 12.

IMD 14 generally operates as a therapy device that delivers electricalstimulation therapy to patient 12 by generating and delivering aprogrammable electrical stimulation signal (e.g., in the form ofelectrical pulses or a continuous waveform) to target therapy sitesproximate electrodes of leads 16, 18. In the example shown in FIG. 1,the electrodes of each lead 16, 18 are disposed proximate to a distalend of the respective lead 16, 18. The target tissue sites can be, forexample, proximate a spinal nerve, a sacral nerve, a pudendal nerve,dorsal genital nerve, a tibial nerve, an inferior rectal nerve, aperineal nerve, or branches of any of the aforementioned nerves. Thetarget tissue sites are selected based on the type of bladderdysfunction (or other patient condition) for which therapy system 10 isimplemented to treat.

In some examples, the target tissue sites can be identified prior toimplantation of leads 16, 18. For example, a device, such as anintroducer or needle, can be introduced into patient 12 and a testelectrical signal can be delivered to tissue of patient 12 via thedevice. The device may be moved within patient 12 until a desirablephysiological response is elicited by the test electrical signal, whichcan indicate that the device (e.g., the one or more electrodes used todeliver the test stimulation) is positioned at a tissue site thatcaptures a target nerve. In some examples, the physiological responsemay be detected through a motor response that may be visually detected,a sensory response as reported by the patient, or through an electricalresponse e.g., sensed nerve signals). Electrodes of leads 16, 18 cansubsequently be positioned at the tissue site at which the testelectrical signal elicited the desirable physiological response. Inother examples, the test stimulation may be delivered via leads 16, 18.

IMD 14 may be surgically implanted in patient 12 at any suitablelocation within patient 12, such as in the side of the lower abdomen orthe side of the lower back or upper buttocks, IMD 14 can include abiocompatible outer housing, which may be formed from titanium,stainless steel, a liquid crystal polymer, or the like. One or moremedical leads, e.g., leads 16, 18, may be connected to IMD 14 andsurgically or percutaneously tunneled to place one or more electrodes ofthe respective lead at a target tissue site proximate to a desired nerveor muscle, e.g., one of the previously listed target therapy sites, suchas a tissue site proximate a spinal, sacral or pudendal nerve. Theproximal ends of leads 16, 18 are both electrically and mechanicallycoupled to IMD 14 either directly or indirectly, e.g., via respectivelead extensions.

Electrical conductors disposed within the lead bodies of leads 16, 18electrically connect electrodes of the respective lead to a therapydelivery module (e.g., a stimulation generator) of IMD 14. In addition,in some examples, the electrical conductors of leads 16, 18 electricallyconnect the electrodes of the respective lead to a sensing module of IMD14, which enables IMD 14 to sense a physiological parameter of patient12 via the electrodes.

A midline of patient 12 divides a body of patient 12 into two lateralsides, which can be referred to as a left side and a right side. Spinalcord 24 of patient 12 is approximately positioned at the midline ofpatient 12, such that one lateral side of patient 12 may be consideredto be on one side of spinal cord 24 and the other lateral side ofpatient 12 may be considered to be on other side of spinal cord 24. Atleast some of the nerves innervating the pelvic floor of patient 12, aswell as other nerves of patient 12, comprise left and right branches (orportions) on respective lateral sides of patient 12. In the exampleshown in FIG. 1, leads 16, 18 are positioned to deliver stimulation totarget tissue sites on respective lateral sides of patient 12, such thattherapy system 10 is configured to deliver bilateral stimulation topatient 12 via electrodes of leads 16, 18. In this way, IMD 14 maydeliver bilateral stimulation to patient 12 by delivering stimulation totarget tissue sites on opposite sides of the midline of patient 12 viaelectrodes positioned on respective lateral sides of patient 12. Forexample, IMD 14 may deliver stimulation to a first lateral side ofpatient 12 via a first set of electrodes positioned on the first lateralside of patient (e.g., proximate a nerve or nerve branch on the firstlateral side) and deliver stimulation to a second lateral side ofpatient 12 via a second set of electrodes (different than the first set)positioned on the second lateral side of patient (e.g., proximate anerve or nerve branch on the second lateral side). In some examples, thetarget tissue sites are selected such that delivery of stimulation tothe target tissue sites either at different times or substantiallysimultaneously provides an inhibitory physiological response related tovoiding of patient 12, such as a reduction in a frequency of bladdercontractions.

In some examples, when IMD 14 delivers bilateral stimulation to patient12, IMD 14 delivers electrical stimulation to both lateral sides ofpatient 12 to achieve a desired therapeutic effect, such as a reductionin bladder contraction frequency. The stimulation delivered to bothlateral sides of the patient works together (e.g., in a synergisticfashion) to provide a common therapeutic effect. Thus, regardless ofwhether IMD 14 delivers bilateral stimulation by delivering electricalstimulation to the two lateral sides of patient 12 at different times(e.g., non-overlapping pulse trains, stimulation periods, “on cycles” orany combination thereof) or at substantially simultaneously (e.g., atleast partially overlapping pulse trains, stimulation periods, “oncycles” or any combination thereof), the desired therapeutic effect maybe elicited by the stimulation to both lateral sides of the patient. Insome cases, the desired therapeutic effect may not be elicited withoutthe electrical stimulation delivery to both lateral sides of patient 12.In contrast to bilateral stimulation, when IMD 14 delivers unilateralstimulation, IMD 14 delivers electrical stimulation to only one lateralside of patient 14 to achieve a desired therapeutic effect. Withunilateral stimulation, the therapeutic effect is elicited by thestimulation delivered to only one lateral side of the patient 12, andstimulation need not be delivered to both lateral sides of patient 12 toachieve the desired therapeutic effect.

Leads 16, 18 can be positioned to deliver stimulation to target tissuesites proximate branches of the same nerve or branches of differentnerves. For example, IMD 14 can deliver bilateral stimulation to patient12 by delivering stimulation to both the left and right nerve branches(or portions) of the same nerve and/or by delivering stimulation to aleft branch of a first nerve and a right branch of a second nerve thatis different than the first nerve. As an example, leads 16, 18 can bepositioned to deliver electrical stimulation to tissue sites on bothlateral sides of patient 12 to modulate activity of both a left and aright sacral nerve or nerve portion, both a left and a right pudendalnerve or nerve portion, and/or both a sacral nerve or nerve portion anda pudendal nerve or nerve portion on different lateral sides of patient12. The target tissue sites on the two lateral sides of patient 12 canbe target tissue sites proximate to branches of the same nerve orbranches of different nerves. In addition, IMD 14 can deliver bilateralstimulation to patient 12 via a subset of electrodes of both leads 16,18, e.g., electrodes of each lead 16, 18 can be positioned on adifferent lateral side of patient 12 or one or both of the leads 16, 18can be positioned such that electrodes of the respective lead arelocated on both lateral sides of patient 12.

It is believed that electrical stimulation of bilateral spinal nervesmay produce a stronger inhibition of bladder contractions thanunilateral nerve stimulation alone. Techniques for controlling deliveryof bilateral stimulation to patient 12 to manage bladder dysfunction aredescribed herein. In some examples, IMD 14 delivers a first stimulationtherapy to patient 12, and, upon detecting a trigger event, delivers asecond stimulation therapy to patient 12. Thus, the second stimulationtherapy is delivered to patient 12 in a closed loop or a pseudo-closedloop manner in these examples because the initiation of the delivery ofthe second stimulation therapy is dependent upon detection of a triggerevent. As discussed in further detail below, the trigger event thattriggers the delivery of the second stimulation therapy can include, forexample, detection of a physiological condition indicative of anincreased possibility of an involuntary voiding event (e.g., relative toa baseline or another previously determined condition) or an imminentinvoluntary voiding event, input from the patient (or a patientcaretaker) that indicates that additional therapy to help prevent theoccurrence of an involuntary voiding event is desirable, a time of day,and/or expiration of a timer. The duration of the timer can be, forexample, based on a bladder fill cycle of the patient, which isdiscussed in further detail below. In some examples, the timer isstarted at a beginning of the patient's bladder fill cycle, such asimmediately after patient 12 voids.

The first and second stimulation therapies both include bilateralstimulation to patient 12, but the coordination of stimulation to thelateral sides of patient 12 differs between the first and secondstimulation therapies. The coordination may include, for example, theextent to which a stimulation period for electrical stimulationdelivered to a first lateral side of the patient overlaps with astimulation period for electrical stimulation delivered to a secondlateral side of the patient. The stimulation period may be, for example,the period of time during which IMD 14 is actively deliveringstimulation to patient 12, such as in the form of an electricalstimulation train (e.g., a waveform or pulse train). The stimulationsignals during the stimulation period may not be continuous (e.g., maybe delivered in bursts of continuous time signals or pulses, or in aplurality of pulses separated in time). However, the stimulation periodrepresents the period of time during which IMD 14 is actively generatingand delivering stimulation to a particular lateral side of patient 12.

In some cases, the coordination includes, for example, the extent towhich electrical stimulation trains delivered to each lateral side ofpatient 12 overlap. In some examples, an electrical stimulation train isdefined by the electrical stimulation signals delivered to patient 12(e.g., to one lateral side of patient 12) to elicit a desiredtherapeutic effect. In the case of electrical stimulation pulses, theelectrical stimulation signal train may be referred to as a “pulsetrain” and may include, for example, a plurality of pulses (e.g., atleast two pulses) separated in time. The period of time between thestart of consecutive pulses in the pulse train may be referred to as apulse period. In some examples, two or more pulse periods may beconsidered to be part of a common pulse train, as well as part of acommon stimulation period. In the case of continuous time pulses, theelectrical stimulation signal train may include a plurality ofstimulation signal cycles (e.g., at least two cycles, such as at leasttwo sine waves). In some examples, two or more stimulation signal cyclesmay be considered to be part of a common stimulation signal train, aswell as part of a common stimulation period. In either the case ofcontinuous time signals or pulses, the electrical stimulation signaltrain may have a specific duration, which may be equal to, for example,a stimulation period during which IMD 14 delivers electrical stimulationto the respective lateral side of patient 12.

It is believed that the manner in which the electrical stimulation iscoordinated between the lateral sides of patient 12 may affect theefficacy of the stimulation therapy, e.g., because the timing of thestimulation delivery between the two lateral sides of patient 12 mayaffect the strength of the physiological response elicited by thebilateral stimulation or the timing with which the physiologicalresponse is observed. This may be at least partially attributable to thespatial summation of the physiological effects of the electricalstimulation therapy. As discussed in further detail below, the secondstimulation therapy may elicit a greater physiological response relatedto bladder dysfunction and/or a more immediate physiological responsefrom patient 12.

The first stimulation therapy includes the delivery of bilateralstimulation to target tissue sites on both lateral sides of patient 12,where the stimulation is delivered to the lateral sides at differenttimes (e.g., in a time interleaved manner). In the example shown in FIG.1, the target tissue sites are selected to be a tissue site that helpsmanage the bladder dysfunction of patient 12. In some examples, thetarget tissue is proximate to at least one of a spinal nerve, a sacralnerve, a pudendal nerve, dorsal genital nerve, a tibial nerve, aninferior rectal nerve, a perineal nerve, or a branch thereof. In someexamples of the first stimulation therapy, IMD 14 does not activelydeliver stimulation signals to the first and second lateral sides ofpatient 12 at the same time. While post-stimulation effects generated bydelivery of stimulation to tissue sites on the first and second lateralsides of patient 12 may be observed at substantially the same time inresponse to the first stimulation therapy, the stimulation trainsdelivered to the first and second lateral sides do not overlap in timein these examples. In these examples, IMD 14 terminates delivery ofstimulation signals to one lateral side before initiating delivery ofstimulation signals to the other lateral side of patient 12.

In some examples, IMD 14 delivers the first stimulation therapy byalternating delivery of stimulation to a first target tissue site on afirst lateral side of patient 12 and a second target tissue site on asecond lateral side of patient 12, such that IMD 14 delivers pulsetrains to respective lateral sides of patient 12 at different,non-overlapping times. As an example, IMD 14 may deliver a first pulsetrain to a first lateral side of patient 12 during a first stimulationperiod, and at the end of the first stimulation period, cease deliveryof stimulation to the first lateral side and initiate delivery of asecond pulse train to a second lateral side of patient 12 during asecond stimulation period. During the second stimulation period, IMD 14does not deliver stimulation to the first lateral side of the patient,and during the first stimulation period, IMD 14 does not deliverstimulation to the second lateral side of the patient. Delivery ofstimulation signal trains to the lateral sides of patient 12 in thisnon-overlapping manner may repeat for as long of a stimulation period asdesired. Alternating delivery of stimulation to the lateral sides ofpatient 12 may help reduce the amount of stimulation delivered to asingle tissue site of patient 12, which may extend the total duration oftherapeutic benefit to patient 12 provided by therapy system 10, e.g.,by reducing patent adaptation.

Reducing the amount of stimulation delivered to a single tissue site inpatient may help reduce neuron habituation or other forms of patientadaptation to the stimulation therapy and extend an effective lifetimeof the stimulation therapy (e.g., the time for which the stimulationtherapy is efficacious in reducing bladder contraction frequency). Ithas been found that patient 12 may adapt to stimulation delivered by IMD14 over time, such that a certain level of electrical stimulationprovided to a tissue site in patient 12 may be less effective over time.This phenomenon may be referred to as “adaptation.” As a result, anybeneficial effects to patient 12 from the electrical stimulation maydecrease over time. While the electrical stimulation levels (e.g.,amplitude of the electrical stimulation signal) may be increased toovercome such adaptation, the increase in stimulation levels may consumemore power, and may eventually reach undesirable levels of stimulation.Delivery of bilateral stimulation to patient 12 in an alternatingfashion may help reduce the adaptation

The alternating stimulation delivered to the first and target tissuesites can be substantially balanced in some examples, e.g., IMD 14delivers stimulation having substantially similar stimulationintensities to the two lateral sides of patient 12 and/or IMD 14delivers stimulation to both lateral sides of patient 12 forsubstantially equal amounts of time. Substantial similarity in theintensity of stimulation may be indicated by, for example, substantiallysimilar stimulation signals. Stimulation intensity may be affected by,for example, a current amplitude of the stimulation signal, a voltageamplitude of the stimulation signal, a frequency of the stimulationsignal, a pulse rate of the stimulation signal, a pulse width of thestimulation signal, the shape of the stimulation signal, the duty cycleof the stimulation signal, or the combination of electrodes with whichIMD 14 delivers the stimulation to patient 12.

As an example of the substantially balanced bilateral stimulationdelivered to patient 12 in an alternating manner, IMD 14 can deliver apulse train (or waveform) to the first target tissue site on a firstlateral side of patient 12 for a duration of time followed by deliveryof the same stimulation pulse train to the second target tissue site ona second lateral side of patient 12 for the duration of time, followedby delivery of the same stimulation pulse train to the first targettissue site for the duration of time, and so forth. Other techniques fordelivering substantially balanced bilateral stimulation in analternating manner are contemplated.

In other examples, the stimulation delivered to the first and targettissue sites for the first stimulation therapy is imbalanced, e.g., theintensity of stimulation delivered to the two lateral sides of patient12 is different, the stimulation is delivered to each lateral side ofpatient 12 for different durations of time (i.e., the stimulationperiods for the lateral sides are different), or both. As an example ofthe substantially imbalanced bilateral stimulation delivered to patient12 in an alternating manner, IMD 14 can deliver a first stimulationpulse train to the first target tissue site for a first duration of timefollowed by delivery of a second pulse train to the second target tissuesite for a second duration of time, and so forth. In order to achieveimbalanced bilateral stimulation, the stimulation pulses of the firstand second pulse trains can be the same, and the first and seconddurations of time may be different. In other examples, in order toachieve imbalanced bilateral stimulation, the stimulation pulses of thefirst and second pulse trains may be different, and the first and seconddurations of time may be the same or different. Other techniques fordelivering imbalanced bilateral stimulation in an alternating manner arecontemplated.

The second stimulation therapy includes substantially simultaneousbilateral stimulation therapy, whereby IMD 14 delivers stimulation toboth lateral sides of patient 12 at substantially the same time. Duringsubstantially simultaneous bilateral stimulation therapy, the pulsetrains delivered by IMD 14 to respective lateral sides of patient 12 atleast partially overlap. As an example, IMD 14 may deliver a first pulsetrain to a first lateral side of patient 12, and, at the same time,deliver a second pulse train to a second lateral side of patient 12. IMD14 may deliver the first and second pulse trains such that theycompletely overlap (e.g., start and stop at the same time, such that thestimulation periods are the same) or partially overlap (e.g., the firstpulse train may be delivered for a period of time prior to deliveringthe second pulse train, such that the stimulation periods partiallyoverlap). The intensity levels of the stimulation delivered to the twosides of patient are substantially equal in some examples, and aredifferent in other examples. IMD 14 delivers stimulation to a firstlateral side of patient 12 during a first stimulation period anddelivers stimulation to a second lateral side of patient 12 during asecond stimulation period. During the second stimulation therapydelivered by IMD 14, the first and second stimulation periods at leastpartially overlap, such that stimulation is delivered to the first andsecond lateral sides of patient 12 substantially simultaneously.

The second stimulation therapy may not consist substantially entirely ofsubstantially simultaneous bilateral stimulation therapy. For example,IMD 14 may initiate delivery of stimulation to at least one of the firstlateral side or second lateral side of patient 12 prior to initiatingdelivery of stimulation to the other one of the first lateral side orsecond lateral side of patient 12. As another example, the stimulationdelivered to the first and second stimulation periods may periodically,but not entirely, overlap during the delivery of the second stimulationperiod. In other examples, during the second stimulation therapydelivered by IMD 14, the first and second stimulation periodssubstantially completely overlap, such that the second stimulationtherapy consists substantially entirely of substantially simultaneousbilateral stimulation therapy. The first and second stimulation periodsmay be substantially the same in some examples, and may be different inother examples.

In examples in which the stimulation delivered to the lateral sides ofpatient 12 at substantially the same time have substantially similarintensities and are delivered for substantially similar durations oftime (i.e., have substantially similar stimulation periods), thesubstantially simultaneous bilateral stimulation may be consideredbalanced. Likewise, in examples in which the stimulation delivered tothe lateral sides of patient 12 at substantially the same time have atleast one of different similar intensities and or different stimulationperiods, the substantially simultaneous bilateral stimulation may beconsidered imbalanced.

In the first and second stimulation therapies, the intensity ofstimulation that is delivered to patient 12 can be lower than,substantially equal to, or greater than a threshold stimulationintensity level (also referred to herein as a “threshold intensity” or“threshold intensity level”) for patient 12. The threshold stimulationintensity level may be the stimulation intensity level at which anacute, physiologically significant response (also referred to herein asa threshold physiological response) of patient 12 is first observed whenincreasing the stimulation intensity from a low intensity to a higherintensity. Stated another way, the threshold stimulation intensity levelmay be defined as approximately the lowest stimulation intensity levelthat elicits an acute, physiologically significant response of patient12. The acute, physiologically significant response may or may not beperceived by patient 12. In some examples, an acute response may bedefined as a physiological response that occurs within about 30 seconds(e.g., about 10 seconds) of patient 12 receiving the stimulation.

The sufficiency of the stimulation in producing an acute physiologicalresponse and/or desired therapeutic effect may be a function ofstimulation intensity and time for which stimulation is delivered.Stimulation intensity may be, in turn, a function of one or moreparameters. In the case of stimulation pulses, stimulation intensity maybe a function of current of voltage pulse amplitude, pulse rate, andpulse width. The desired therapeutic effect is different from the acutephysiological response. As one illustration, the desired therapeuticeffect may be a reduction in the frequency of bladder contractions inthe patient, whereas the acute physiological response may be a motorfunction caused by the stimulation.

The physiologically significant response used to determine the thresholdintensity level can be any suitable physiological response, which may beselected by, e.g., patient 12 or a clinician. The physiological responseof interest may be, for example, a patient perception (e.g., thethreshold intensity level may be a patient perception threshold), amotor response (e.g., the threshold intensity level may be a motorthreshold), a response indicative of capture of a nerve (e.g., thethreshold intensity level may be a nerve capture threshold). The nervecapture can be detected using any suitable technique, such as, e.g.,sensing afferent or efferent nerve signals via electrodes implanted inpatient 12 or external to patient 12 when the stimulation is deliveredto patient 12. Other types of physiological responses may be detectedand may be unrelated to the type of therapy for which therapy system 10delivers therapy in some examples. For example, a toe twitch may beconsidered to be a physiological response that is indicative of astimulation threshold intensity, but the toe twitch may be a responsethat does not provide efficacious therapy to patient 12.

In other examples, the physiological response may be related to the typeof therapy for which therapy system 10 delivers therapy. For example,the physiological response may be an acute reduction in bladdercontraction frequency or intensity. The threshold intensity level,however, may not be the same as a therapy threshold, e.g., a stimulationintensity at which IMD 14 provides efficacious therapy to patient 12 tomanage the patient condition (e.g., to reduce bladder contractionfrequency).

Whether or not a physiological response is considered to bephysiologically significant can be determined by patient 12, aclinician, or another suitable person or device. As an example, thestimulation may elicit movement of a toe of patient 12, and patient 12may define the movement of the toe as physiologically significant whenthe movement of the toe is perceptible or when the movement of the toeis above some arbitrary amount defined by patient 12 or the clinician.

In some examples, the first and second stimulation therapies areconfigured to elicit similar inhibitory physiological responses (e.g., areduction in bladder contraction frequency) from patient 12 related tovoiding, e.g., to reduce a bladder contraction frequency. However, therelative strength of the inhibitory physiological response elicited bythe first and second stimulation therapies may differ. In some examples,the second stimulation therapy elicits a more immediate inhibitoryphysiological response compared to the first stimulation therapy, and,in some cases, a stronger inhibitory physiological response than thefirst stimulation therapy. Otherwise stated, the second stimulationtherapy may elicit a more acute physiological response from patient 12that helps minimize the likelihood of an occurrence of an involuntaryvoiding event, where the acute response may be observed in a shorteramount of time compared to the physiological response elicited from thedelivery of the first stimulation therapy. In this way, the secondstimulation therapy may provide more efficacious therapy than the firststimulation therapy in some situations, such as when a patient conditionindicative of an increased possibility of an involuntary voiding eventor an imminent involuntary voiding event is detected.

In examples in which the inhibitory physiological response includes areduction in bladder contraction frequency, the reduction in bladdercontraction frequency resulting from the delivery of the secondstimulation therapy may be greater that the reduction in bladdercontraction frequency resulting from delivery of the first stimulationtherapy. In this way, a second inhibitory physiological responseelicited by the delivery of the second stimulation therapy may begreater (or stronger) than a first inhibitory physiological responseelicited by the delivery of the first stimulation therapy.

In some examples, the first stimulation therapy produces a relativelymoderate inhibitory physiological response compared to the secondstimulation therapy. In some examples, the inhibitory physiologicalresponse elicited by the first stimulation therapy is observed duringthe stimulation period (also referred to herein as a first time period)in which IMD 14 delivers the first stimulation therapy to patient 12.This physiological response may also be observed during apost-stimulation period (also referred to herein as a second timeperiod) in some examples. IMD 14 does not deliver the first stimulationtherapy to patient 12 during the post-stimulation period, and, in someexamples, does not deliver any therapy to patient 12 during thepost-stimulation period.

In some examples, the physiological response to stimulation may be morepronounced during the post-stimulation period that immediately followsthe stimulation period. For example, the delivery of the firststimulation therapy by IMD 14 may elicit an inhibitory physiologicalresponse related to a voiding event during a stimulation period and apost-stimulation period, and the inhibitory physiological responseduring the post-stimulation period may be greater than the inhibitoryphysiological response during the stimulation period. When theinhibitory physiological response includes a reduction in bladdercontraction frequency, for example, the delivery of the firststimulation therapy can reduce the bladder contraction frequency duringthe stimulation period and the post-stimulation period, where thereduction in bladder contraction frequency is greater during thepost-stimulation period.

In other examples, the inhibitory physiological response evoked by thefirst stimulation therapy may not be observed immediately upon thedelivery of the first stimulation therapy, but, rather, may be observedduring the post-stimulation period. Thus, the first stimulation therapymay elicit an inhibitory physiological response related to voidingduring a post-stimulation period, and may not elicit an inhibitoryphysiological response related to voiding while IMD 14 during astimulation period.

IMD 14 may deliver the first stimulation therapy in an open loop mannerin some examples, in which IMD 14 delivers the first stimulation therapywithout intervention from a user or a sensor. For example, if the firststimulation therapy elicits a delayed physiological response that isobserved during a second time period that immediately follows a firsttime period during which stimulation is delivered to patient 12, IMD 14can deliver the first stimulation therapy to patient 12 as a periodicrepetition of the first time period and second time period. In otherexamples, IMD 14 may deliver the first stimulation therapy in a closedloop manner. For example, IMD 14 deliver the first stimulation therapyfor the first time period, and cease delivery of the first stimulationtherapy until a certain bladder contraction frequency is detected. Anexample of closed-loop delivery of the first stimulation therapy isdescribed below with respect to FIG. 8.

In accordance with some examples of the disclosure, IMD 14 delivers thefirst stimulation therapy to patient 12 over an extended period of time,e.g., chronic stimulation, and delivers the second stimulation therapyto patient 12 when a stronger therapy is needed or desirable. Thus, insome cases, the second stimulation therapy may be referred to as anacute therapy or a temporary therapy because the second stimulationtherapy is delivered for only periodically relative to the firststimulation therapy, e.g., as needed, rather than on a regular basis. Bylimiting the delivery of substantially simultaneous bilateralstimulation therapy, the amount of therapy delivered to patient 12 islimited compared to examples in which the substantially simultaneousbilateral stimulation is delivered to patient continuously and not basedon a detected trigger event. Reducing the overall amount of stimulationdelivered to patient 12 may help reduce neuron habituation or otherforms of patient adaptation to the stimulation therapy and extend aneffective lifetime of the stimulation therapy (e.g., the time for whichthe stimulation therapy is efficacious in reducing bladder contractionfrequency).

In some examples, IMD 14 delivers the first and second stimulationtherapies in different time slots, i.e., on a time-interleaved basis,such that IMD 14 only delivers one type of stimulation therapy at atime. In these examples, IMD 14 may deliver the first stimulationtherapy, and, when triggered, deactivate delivery of the firststimulation therapy and activate delivery of the second stimulationtherapy. IMD 14 may deliver the second stimulation therapy for apredetermined duration of time, referred to herein as a therapy period,for a duration of time controlled by patient 12, or until a specificpatient event is detected (e.g., voluntary voiding). In these examples,after delivering the second stimulation therapy, IMD 14 may revert backto delivering the first stimulation therapy until another trigger eventfor activating the delivery of the second stimulation therapy isdetected.

As discussed above, a trigger event can include, for example, detectionof a physiological condition indicative of an increased possibility ofan involuntary voiding event or an imminent involuntary voiding event,input from the patient (or a patient caretaker) that indicates thatadditional therapy to help prevent the occurrence of involuntary voidingevent is desirable, or expiration of a timer comprising a predeterminedduration of time. Any one or more of the trigger events may beimplemented by IMD 14 to control the timing of the second stimulationtherapy. The trigger event is different from the thresholds or otherparameters used to control closed loop delivery of the first stimulationtherapy.

In examples in which the trigger event comprises a physiologicalcondition of patient 12, IMD 14 may detect the physiological conditionbased on a physiological parameter of patient 12 sensed by, e.g., viasensor 22 or a sensing module of IMD 14. An example of a trigger eventcomprising a physiological condition is a bladder volume (e.g., asindicated by an impedance of the bladder of patient 12, pressure sensedat a bladder wall, the output of a strain gauge on the bladder wall, andthe like) that is indicative of an increased possibility of aninvoluntary voiding event. Another example of a trigger event comprisinga physiological condition is a bladder contraction intensity or bladdercontraction frequency at or above a trigger event threshold. The triggerevent threshold is selected to be a level that is indicative of anincreased possibility of an involuntary voiding event, e.g., relative toa patient condition for which the first stimulation therapy isappropriate.

IMD 14 may detect contractions of bladder based on any suitablephysiological parameter such as, but not limited to, bladder impedance,bladder pressure, pudendal or sacral afferent nerve signals, anelectromyogram (EMG) of a relevant muscle (e.g., a urinary sphinctermuscle, bladder wall or detrusor muscle), or any combination thereof.Thus, sensor 22 may include, for example, a pressure sensor positionedin patient 12 to detect changes in bladder pressure, electrodes forsensing pudendal or sacral afferent nerve signals, electrodes forsensing urinary sphincter EMG signals (or anal sphincter EMG signals inexamples in which therapy system 10 provides therapy to manage fecalurgency or fecal incontinence), or any combination thereof. In examplesin which IMD 14 detects bladder contractions or a bladder volume (alsoreferred to herein as a fill level) based on an impedance through thebladder of patient 12, which varies as a function of the contraction ofthe bladder, IMD 14 can determine the impedance through the bladderusing the sensing configuration shown and described below with respectto FIG. 16.

As shown in FIG. 1, in some examples, sensor 22 can be physicallyseparate from IMD 14 and can wirelessly transmit signals to IMD 14.Alternatively sensor 22 may be carried on one of leads 16, 18 or anadditional lead coupled to IMD 14. In some examples, sensor 22 mayinclude one or more electrodes for sensing afferent nerve signals or oneor more sense electrodes for generating an EMG of a relevant muscle.

One type of bladder contraction detection algorithm indicates anoccurrence of a bladder contraction when a signal generated by sensor 22(or a sensing module of IMD 14 or another sensing module) exhibits acertain characteristic, which may be a time domain characteristic (e.g.,a mean, median, peak or lowest signal amplitude within a particular timeperiod) or a frequency domain characteristic (e.g., an energy level inone or more frequency bands or a ratio of energy levels in differentfrequency bands). Another bladder contraction detection algorithmindicates the occurrence of a bladder contraction if a sensed signalsubstantially correlates to a signal template, e.g., in terms offrequency, amplitude and/or spectral energy characteristics. IMD 14 mayuse known techniques to correlate a sensed signal with a template inorder to detect the bladder contraction or detect the bladdercontraction based on the frequency domain characteristics of a sensedsignal. Other bladder contraction techniques may be used.

In addition to or instead of the previously discussed physiologicalconditions, the trigger event can be a patient activity level (e.g., anindication of the level of motion or movement of one or more of thepatient's limbs or trunk) or patient posture state that is indicative ofan increased probability of an occurrence of an involuntary voidingevent. Sensor 22 may comprise, for example, a patient motion sensor,such as a two-axis accelerometer, three-axis accelerometer, one or moregyroscopes, pressure transducers, piezoelectric crystals, or othersensor that generates a signal that changes as patient activity level orposture state changes. In some examples, IMD 14 controls the delivery ofthe second stimulation therapy to patient 12 upon detecting a patientactivity level exceeding a particular threshold based on the signal fromthe motion sensor. The patient activity level that is greater than orequal to a threshold (which may be stored in a memory of IMD 14,programmer 20 or another device) may indicate that patient 12 isengaging in an activity that may increase the possibility of anoccurrence of an involuntary voiding event, and, therefore, the greaterinhibition of bladder contraction frequency provided by the secondstimulation therapy may be desirable while patient 12 is engaging in theactivity. In this way, the second stimulation therapy provided by IMD 14may be useful for providing responsive stimulation therapy that adaptsthe intensity of stimulation to the circumstances that may affectpatient incontinence and provide an additional layer of therapy to helpprevent the occurrence of an involuntary voiding event.

Instead of or in addition to the activity level of patient 12, IMD 14can control the delivery of the second stimulation therapy to patient 12upon detecting a posture state associated with a relatively highprobability of an occurrence of an involuntary voiding event (comparedto other posture states) based on the signal from sensor 22. Forexample, patient 12 may be more prone to an involuntary voiding eventwhen patient 12 is in an upright posture state compared to a lying downposture state. IMD 14 may, for example, store a plurality of motionsensor signals and associate the signals with particular patient posturestates using any suitable technique. IMD 14 may flag some of the posturestates as being posture states for which additional therapy (e.g.,delivery of the second stimulation therapy) to help prevent theoccurrence of an incontinence event is desirable.

In some examples, the delivery of the second stimulation therapy isinitiated based on a time of day, which can be predetermined and storedby IMD 14. The time of day at which IMD 14 initiates the delivery of thesecond stimulation therapy can be, for example, associated with a timeof day at which patient 12 is more active, such that the additionallayer of therapy to help prevent in involuntary voiding event may bedesirable. As an example, IMD 14 may deliver the first stimulationtherapy while patient 12 is sleeping (the sleep times can be associatedwith predetermined times of day in some examples or the sleep can bedetected based on one or more patient parameters), and then initiate thedelivery of the second stimulation therapy when patient 12 is awake. Inother examples, the times of day at which IMD 14 initiates the deliveryof the second stimulation therapy may be selected to be at regular orirregular time intervals. In addition, in other examples, the times ofday at which IMD 14 initiates the delivery of the second stimulationtherapy can be selected to be a time at which the patient's pelvic floormuscles may be more tired, which may increase the possibility of in anoccurrence of an involuntary voiding event, such that the additionalbladder dysfunction therapy may be desirable.

Another trigger event for initiating the delivery of the secondstimulation therapy can be the expiration of a timer. The tinier used totrigger the second stimulation therapy can be based on, for example, thebladder fill cycle of patient 12. In these examples, IMD 14 can restartthe tinier upon receiving an indication that the bladder fill cycle ofpatient 12 has been restarted, e.g. restarted by occurrence of a voidingevent, which can be voluntary, hut, in some cases, involuntary. At thebeginning of a bladder fill cycle, the bladder of patient 12 issubstantially empty or low, and fills throughout the cycle. The bladderfill cycle restarts upon emptying of the bladder. The duration of thetinier may be selected such that IMD 14 delivers the second stimulationtherapy when the bladder fill level of patient 12 is approximated to beat a level in which additional therapy delivery may be desirable to helpreduce the possibility of the occurrence of an involuntary voidingevent. For example, the duration of the timer may be about 50% to about75% of the way through the bladder fill cycle for patient 12, althoughother durations can be used and can depend upon the severity of thepatient's bladder dysfunction.

The bladder fill cycle that is used to select the timer duration can bespecific to patient 12 or based on a plurality of patients, e.g., withsimilar bladder dysfunction disorders. In some examples, the duration ofthe tinier is selected based on the mean, median, or shortest bladderfill cycle duration of patient 12 during a certain period of time (e.g.,on the order of hours, days, or weeks), which can be prior to anydelivery of stimulation to patient 12, or a time period immediatelypreceding the time at which the timer duration is selected.

In some examples, instead of or in addition to a trigger event detectedbased on input from sensor 22 or expiration of a tinier, the triggerevent can include patient input. Thus, IMD 14 may deliver the secondstimulation therapy in response to receiving patient input. For example,patient 12 can interact with programmer 20 to provide input that causesIMD 14 to deliver the second stimulation therapy. In this way, patient12 may control delivery of the second stimulation therapy. Patient 12may initiate the delivery of the second stimulation therapy for anysuitable reason. In some cases, patient 12 may be afflicted with urgencyor urge incontinence, and upon perceiving an urge to void, patient 12may provide input that causes IMD 14 to deliver the second stimulationtherapy. In this way, therapy system 10 may provide patient 12 withdirect control of the bladder dysfunction therapy.

Programmer 20 is a device configured to communicate with IMD 14, and canbe, for example, a key fob or a wrist watch, handheld computing device,computer workstation, or networked computing device. Programmer 20includes a user interface that receives input from a user (e.g., patient12, a patient caretaker or a clinician). In some examples, the userinterface includes, for example, a keypad and a display, which may forexample, be a cathode ray tube (CRT) display, a liquid crystal display(LCD) or light emitting diode (LED) display. The keypad may take theform of an alphanumeric keypad or a reduced set of keys associated withparticular functions. Programmer 20 can additionally or alternativelyinclude a peripheral pointing device, such as a mouse, via which a usermay interact with the user interface. In some examples, a display ofprogrammer 20 may include a touch screen display, and a user mayinteract with programmer 20 via the display. It should be noted that theuser may also interact with programmer 20 and/or ICD 16 remotely via anetworked computing device.

A user, such as a physician, technician, surgeon, electrophysiologist,or other clinician, may also interact with programmer 20 or anotherseparate programmer (not shown), such as a clinician programmer, tocommunicate with IMD 14. Such a user may interact with a programmer toretrieve physiological or diagnostic information from IMD 14. The usermay also interact with programmer 20 to program IMD 14, e.g., selectvalues for the stimulation parameter values with which IMD 14 generatesand delivers stimulation and/or the other operational parameters of IMD14. For example, the user may use programmer 20 to retrieve informationfrom IMD 14 regarding the bladder contraction frequency of patient 12,bladder cycle durations, and/or voiding events. As another example, theuser may use a programmer to retrieve information from IMD 14 regardingthe performance or integrity of IMD 14 or other components of system 10,such as leads 16, 18, or a power source of IMD 14. In some examples,this information may be presented to the user as an alert if a systemcondition that may affect the efficacy of therapy is detected.

In some examples, patient 12 may interact with programmer 20 to controlIMD 14 to deliver the second stimulation therapy, to manually abort thedelivery of the second stimulation therapy by IMD 14 while IMD 14 isdelivering the second stimulation therapy or is about to deliver thesecond stimulation therapy, or to inhibit the delivery of stimulationtherapy by IMD 14, e.g., during voluntary voiding events.

In addition to or instead of interacting with programmer 20 to controltherapy delivery, in some examples, patient 12 may interact directlywith IMD 14 to control IMD 14 to deliver the second stimulation therapy,manually abort the delivery of the second stimulation therapy, orinhibit the delivery of the stimulation therapy. For example, a motionsensor can be integrated into or on a housing of IMD 14, and the motionsensor can generate a signal that is indicative of patient 12 tappingIMD 14 through the skin. The number, rate, or pattern of taps may beassociated with the different programming capabilities, and MD 14 mayidentify the tapping by patient 12 to determine when patient input isreceived.

In some examples, programmer 20 provides a notification to patient 12when the first and/or second stimulation therapies are being deliveredor notify patient 12 of the prospective delivery of the first and/orsecond stimulation therapies to provide patient 12 with the opportunityto manually abort either the first and/or second stimulation therapy. Insuch examples, programmer 20 may display a visible message, emit anaudible alert signal or provide a somatosensory alert (e.g., by causinga housing of programmer 20 to vibrate). After generating thenotification, programmer 20 may wait for input from patient 12 prior todelivering the stimulation therapy. Patient 12 may enter input thateither confirms delivery of the first or second stimulation therapy ispermitted or desirable, or manually aborts the prospective delivery ofthe first and/or second stimulation therapy. In the event that no inputis received within a particular range of time, programmer 20 may, forexample, wirelessly transmit a signal that indicates the absence ofpatient input to IMD 14. IMD 14 may then elect to deliver or not todeliver the stimulation therapy based on the programming of IMD 14.

In examples in which programmer 20 is configured to inhibit delivery ofthe second stimulation therapy, and, in some cases, the firststimulation therapy, when patient 12 is voluntarily voiding, patient 12may use programmer 20 to enter input that indicates the patient will bevoiding voluntarily. When IMD 14 receives the input from programmer 20,IMD 14 may suspend delivery of the relevant stimulation therapy for apredetermined period of time, e.g., two minutes, to allow patient 12 tovoluntarily void. In some examples, the input from patient 12 thatindicates the voluntary voiding may also be used to determine a durationof a bladder fill cycle of patient 12 and control the delivery of thefirst stimulation therapy, as described with respect to FIG. 6.

IMD 14 and programmer 20 may communicate via wireless communicationusing any techniques known in the art. Examples of communicationtechniques may include, for example, low frequency or radiofrequency(RF) telemetry, but other techniques are also contemplated. In someexamples, programmer 20 may include a programming head that may beplaced proximate to the patient's body near the IMD 14 implant site inorder to improve the quality or security of communication between IMD 14and programmer 20.

In some examples, either IMD 14 or programmer 20 may track when IMD 14delivers the second stimulation therapy to patient 12. Frequent deliveryof the second stimulation therapy may be undesirable because, forexample, muscle fatigue or adaptation to the stimulation therapy mayresult. Frequent delivery of the second stimulation therapy may indicatethat, as another example, the patient's bladder is full. Programmer 20can provide a notification to patient 12 when the second stimulationtherapy is triggered too frequently. The notification may be triggeredbased on any suitable criteria, which may be determined by a clinicianor automatically programmed into IMD 14 or programmer 20. For example,in the event that the second stimulation therapy is triggered five timeswithin five minutes, programmer 20 may provide a notification to patient12 indicating the same. This may allow patient 12 to proceed to abathroom before a leaking episode occurs. The notification provided byprogrammer 20 may also direct patient 12 to voluntarily void.

FIG. 2 is shows a simplified anatomical view of the pelvic floor of afemale human patient, the locations of the left and right pudendalnerves 26, 28, respectively, and associated nerves therein, thepositioning of IMD 14 and leads 16, 18 such that the distal portions ofleads 16, 18 are located near left and right pudendal nerves 26, 28. Asshown in FIG. 2, pudendal nerve or nerve portion 26 innervates thepelvic floor muscle and sphincters. Leads 16, 18 are positioned toprovide bilateral stimulation to patient 12. In the example shown inFIG. 2, electrodes 30 of lead 16 are positioned to deliver stimulationto modulate activity of left pudendal nerve or nerve portion 26 andelectrodes 32 of lead 18 are positioned to deliver stimulation tomodulate activity of right pudendal nerve or nerve portion 28. In otherexamples, electrodes 30, 32 of leads 16, 18, respectively, can bepositioned to deliver electrical stimulation to tissue sites proximateother nerves, such as a sacral nerve, and can each be positionedproximate to different nerves or branches of different nerves.

In the example shown in FIGS. 1 and 2, leads 16, 18 are cylindrical.Electrodes 30, 32 of leads 16, 18, respectively, may be ring electrodes,segmented electrodes, partial ring electrodes or any suitable electrodeconfiguration. Segmented and partial ring electrodes each extend alongan arc less than 360 degrees (e.g., 90-120 degrees) around the outerperimeter of the respective lead 16, 18. In some examples, segmentedelectrodes may be useful for targeting different fibers of the same ordifferent nerves to generate different physiological effects. In otherexamples, one or more of leads 16, 18 may be, at least in part,paddle-shaped (i.e., a “paddle” lead), and may include an array ofelectrodes on a common surface, which may or may not be substantiallyflat.

In some examples, one or more of electrodes 30, 32 may be cuffelectrodes that are configured to extend at least partially around anerve (e.g., extend axially around an outer surface of a nerve).Delivering stimulation via one or more cuff electrodes and/or segmentedelectrodes may help achieve a more uniform electrical field oractivation field distribution relative to the nerve, which may helpminimize discomfort to patient 12 that results from the delivery ofelectrical stimulation therapy. An electrical field may define thevolume of tissue that is affected when the electrodes 30, 32 areactivated. An activation field represents the neurons that will beactivated by the electrical field in the neural tissue proximate to theactivated electrodes.

System 10 shown in FIGS. 1 and 2 is merely one example of a therapysystem that is configured to deliver the first and second stimulationtherapies described herein to patient 12, e.g., to generate aninhibitory physiological response in patient 12 to manage a bladderdysfunction of patient 12. Systems with other configurations of leads,electrodes, and sensors are possible. For example, in otherimplementations, IMD 14 may be coupled to additional leads or leadsegments having one or more electrodes positioned at different locationsproximate the spinal cord or in the pelvic region of patient 12. Theadditional leads may be used for delivering different stimulationtherapies to respective stimulation sites within patient 12 or formonitoring at least one physiological parameter of patient 12.

Additionally, in other examples, a system may include more than one IMD.For example, a system may include two IMDs coupled to respective one ormore leads. Each IMD can deliver stimulation to a respective lateralside of patient 12 in some examples. In addition, sensor 22 can beexternal to patient 12 or incorporated into a common housing as IMD 14in some examples, and multiple sensors can be used to sense aphysiological parameter of patient 12.

As another example configuration, a therapy system can include one ormore microstimulators in addition to IMD 14 and leads 16, 18. Themicrostimulators can have a smaller form factor than IMD 14 and may notbe coupled to any separate leads. Rather, the microstimulators can beleadless and configured to generate and deliver electrical stimulationtherapy to patient 12 via one or more electrodes on an outer housing ofthe microstimulators. The microstimulators can be implanted at variouslocations within the pelvic floor and at different target tissue siteswithin patient 12, which are selected such that one or moremicrostimulators can deliver stimulation therapy to target tissue siteson different lateral sides of patient 12. IMD 14 or anothermicrostimulator may act as a “master” module that coordinates thedelivery of stimulation to patient 12 via the plurality ofmicrostimulators.

Although a female patient is depicted with reference to FIG. 2, in otherexamples, the therapy system and regimen described herein may also beused to treat male patients.

FIG. 3 is a block diagram illustrating example components of IMD 14. Inthe example of FIG. 3, IMD 14 includes processor 40, stimulationgenerator 42, memory 44, telemetry module 46, and power source 48. Inother examples, IMD 14 may include a fewer or greater number ofcomponents. For example, in some examples, sensor 22 can be a part ofIMD 14 and substantially enclosed within the same outer housing asstimulation generator 42.

In the example shown in FIG. 3, leads 16, 18 are electrically coupled tostimulation generator 42, such that stimulation generator 42 can deliverelectrical stimulation signals to patient 12 via any subset ofelectrodes 30A-30D (collectively referred to as “electrodes 30”) of lead16 and electrodes 32A-32D (collectively referred to as “electrodes 32”)of lead 18. In some examples, as described above with respect to FIG. 1,each set of electrodes 30, 32 is positioned on opposite sides of amidline of patient 12 to deliver electrical stimulation to respectivelateral sides of patient 12. A proximal end 16A, 18A of each lead 16,18, respectively, extends from the housing of IMD 14 and a distal end16B, 18B of each lead 16, 18, respectively, extends to a target therapysite. If therapy system 10 is used to treat bladder dysfunction, thetarget tissue sites can be, for example, proximate a sacral nerve, apudendal nerve, a tibial nerve, a dorsal genital nerve, an inferiorrectal nerve, a perineal nerve, a hypogastric nerve, a urinarysphincter, or any combination thereof.

In general, IMD 14 comprises any suitable arrangement of hardware, aloneor in combination with software and/or firmware, to perform thetechniques attributed to IMD 14 and processor 40, stimulation generator42, and telemetry module 46 of IMD 14. In various examples, processor 40can include any one or more microprocessors, digital signal processors(DSPs), application specific integrated circuits (ASICs), fieldprogrammable gate arrays (FPGAs), or any other equivalent integrated ordiscrete logic circuitry, as well as any combinations of suchcomponents. IMD 14 may also include a memory 44, which include anyvolatile or non-volatile media, such as a random access memory (RAM),read only memory (ROM), non-volatile RAM (NYRAM), electrically erasableprogrammable ROM (EEPROM), flash memory, and the like. Althoughprocessor 40, stimulation generator 42, and telemetry module 46 aredescribed as separate modules, in some examples, processor 40,stimulation generator 42, and telemetry module 46 can be functionallyintegrated. In some examples, processor 40, stimulation generator 42,telemetry module 46 correspond to individual hardware units, such asASICs, DSPs, FPGAs, or other hardware units.

Memory 44 stores stimulation therapy programs 50 that specifystimulation parameter values for the stimulation therapy provided by IMD14. In some examples, stimulation therapy programs 50 includestimulation therapy programs for the first stimulation therapy and thesecond stimulation therapy. In some examples, memory 44 also storesbladder data 52, which processor 40 may use for controlling the timingof the delivery of the stimulation therapy. For example, bladder data 52can include parameters for detecting bladder conditions (e.g., volume orcontractions) and trigger events, e.g., patient conditions for which thedelivery of the second stimulation therapy is desirable. Example valuesinclude, for example, threshold values or baseline values for at leastone of bladder impedance, bladder pressure, sacral or pudendal afferentnerve signals, bladder contraction frequency, or external urinarysphincter EMG templates. As described in further detail below, thethreshold values and baseline values may indicate a particular event,such as a bladder contraction or a condition indicative of avoiding-related physiological condition (e.g., a patient state in whichthere is a relatively high likelihood of an involuntary voiding event).Other example values that processor 40 can use to detect trigger eventsinclude a time of day or a timer duration, which, as described abovewith respect to FIG. 1, can be based on a bladder fill cycle of patient12.

Bladder data 52 can also include information related to sensed bladdercontractions, bladder impedance and/or posture of patient 12, which maybe recorded for long-term storage and retrieval by a user, or used byprocessor 40 for adjustment of stimulation parameters, such asamplitude, pulse width, and pulse rate. Memory 44 may also storeinstructions for execution by processor 40, in addition to stimulationtherapy programs 50 and bladder data 52. In some examples, memory 44includes separate memories for storing instructions, electrical signalinformation, stimulation therapy programs, and bladder data.

Stimulation generator 42 delivers electrical stimulation to tissue ofpatient 12 via selected electrodes 30, 32 carried by leads 16, 18,respectively. In some examples, processor 40 controls stimulationgenerator 42 by selectively accessing and loading at least one ofstimulation therapy programs 50 from memory 44 to stimulation generator42. In some cases, a clinician or patient 12 may select a particular oneof stimulation therapy programs 50 from a list using a programmingdevice, such as programmer 20 or a clinician programmer. Processor 40may receive the selection via telemetry module 46. In the example shownin FIG. 1 in which one IMD 14 delivers bilateral stimulation to patient12 at different times or at substantially the same time, stimulationgenerator 42 can include at least two independently controllablestimulation channels. The independently controllable channels permitsstimulation delivered to the lateral sides of patient 12 can beunilaterally adjusted as needed. In other examples, such as examples inwhich separate IMDs deliver stimulation to respective lateral sides ofpatient 12, the IMD can include one or more independently controllablestimulation channel.

Stimulation generator 42 generates and delivers stimulation therapy,i.e., electrical stimulation, according to stimulation parameters. Insome examples, stimulation generator 42 delivers therapy in the form ofelectrical pulses. In such examples, relevant stimulation parameters mayinclude a voltage amplitude, a current amplitude, a pulse rate, a pulsewidth, a duty cycle, or the combination of electrodes 30, 32 with whichstimulation generator 42 delivers the stimulation signals to tissue ofpatient 12. In other examples, stimulation generator 42 deliverselectrical stimulation in the form of continuous waveforms. In suchexamples, relevant stimulation parameters may include a voltageamplitude, a current amplitude, a frequency, a shape of the stimulationsignal, a duty cycle of the stimulation signal, or the combination ofelectrodes 30, 32 with which stimulation generator 42 delivers thestimulation signals to tissue of patient 12.

In some examples, the stimulation parameters for the stimulationprograms 50 may be selected to relax the patient's bladder, e.g., toreduce a bladder contraction frequency. An example range of stimulationparameter values for the stimulation therapy that are likely to beeffective in treating bladder dysfunction, e.g., when applied to thespinal, sacral, pudendal, tibial, dorsal genital, inferior rectal, orperineal nerves, are as follows:

-   -   1. Frequency or pulse rate: between about 0.1 Hertz (Hz) and        about 20 Hz.    -   2. Amplitude: between about 0.1 volts and about 50 volts, such        as between about 0.5 volts and about 2.0 volts, or between about        1 volt and about 10 volts. For some patients, the threshold        intensity level may be at an amplitude level less than or equal        to about 2 volts to about 4 volts, though this may differ        between patients. For current controlled systems, the amplitude        may be between about 0.1 milliamps (mA) and about 50 mA, such as        between about 0.5 mA and about 20 mA, or between about 1 mA and        about 10 mA.    -   3. Pulse Width: between about 100 microseconds (μs) and about        400 μs.

Additionally, in some examples, the stimulation parameters for the firststimulation therapy may include the parameters that define the therapycycle, which includes a first time period (“on” periods) during whichIMD 14 actively delivers a stimulation signal to patient 12 and a secondtime period (“off” periods), during which IMD 14 does not deliver anystimulation to patient 12. When stimulation generator 42 delivers thefirst stimulation therapy according to such a therapy cycle, astimulation signal is not continuously delivered to patient 12, butperiodically delivered (e.g., only during the first time period). Asdescribed in further detail below, in some examples, the therapy cycledefines a schedule by which stimulation generator 42 delivers the firststimulation therapy in an open loop manner.

In some examples, the first and second time periods discussed herein mayhave durations on the order of minutes. For example, the first timeperiod, during which IMD 14 delivers the first stimulation therapy, maybe between about 5 minutes and about 20 minutes, such as about 10minutes. In some examples, the second time period, during which IMD 14ceases to deliver the first stimulation therapy, is at least about fiveminutes, such as between about five minutes and about 30 minutes orbetween about 10 minutes and about 20 minutes. In some examples, therelative lengths of the first and second time periods may be selected toprovide advantageous battery life to IMD 14 compared to an IMD 14 thatdelivers stimulation therapy substantially continuously.

The stimulation parameter values for the first stimulation therapy canbe selected, e.g., from the parameter values listed above, such that thefirst stimulation therapy elicits a first inhibitory physiologicalresponse related to voiding of patient 12 during the first time periodand a second inhibitory physiological response related to voiding ofpatient 12 during the second time period. In some examples, the firstand second inhibitory physiological responses related to voiding includea reduction in a bladder contraction frequency, and may differ from eachother by the percentage by which the bladder contraction frequency isreduced. Depending on the stimulation parameter values, the secondphysiological response related to voiding of patient 12 elicited by thefirst stimulation therapy during the second time period can be greaterthan the first physiological response of patient 12. In this way, insome examples, the first stimulation therapy delivered by stimulationgenerator 42 may elicit a post-stimulation inhibitory effect thatextends beyond the first time period, into the second time period.

In some examples, the stimulation parameters are selected such that thefirst stimulation therapy elicits substantially no inhibitoryphysiological response related to voiding of patient 12 during the firsttime period. In other words, the physiological response of patient 12may be substantially similar during the first time period and during atime period prior to the first time period during which stimulationgenerator 42 does not deliver stimulation therapy to patient 12.

At least some of stimulation therapy programs 50 define the firststimulation therapy delivered by IMD 14. Stimulation generator 42 maygenerate the stimulation signals for the first stimulation therapy basedon one stimulation therapy program 50, such that stimulation isdelivered to each lateral side of patient 12 according to the sametherapy program, or based on multiple therapy programs that differ fromeach other by at least one therapy parameter value. For example,stimulation generator 42 may deliver stimulation to a first lateral sideof patient 12 according to a first therapy program and deliverstimulation to a second lateral side of patient 12 at different timesaccording to a second therapy program that differs from the firsttherapy program by at least one therapy parameter value.

Stimulation therapy programs 50 also include therapy programs with whichstimulation generator 42 generates and delivers the second stimulationtherapy delivered by IMD 14. In some examples, stimulation generator 42generates and delivers stimulation signals to both lateral sides ofpatient 12 at the same time based on one stimulation therapy program 50.In other examples, stimulation generator 42 generates and deliversstimulation signals to a first lateral side of patient 12 according toone stimulation therapy program 50 and to the other lateral side ofpatient 12 according to a different stimulation therapy program 50 atsubstantially the same time.

As discussed above, in some examples, stimulation generator 42 generatesand delivers the first stimulation therapy in an open loop manner. Inthese examples, at least some of stimulation therapy programs 50 definevalues for the durations of the first and second time periods. In suchcases, stimulation generator 42 delivers stimulation to patient 12during each of the first time periods according to the same stimulationparameter values. Additionally, the first and second time periodsalternate and each first time period has the same duration and eachsecond time period has the same duration. In some examples, stimulationgenerator 42 continues to deliver stimulation therapy to patient 12according to these stimulation parameters until receiving an instructionfrom processor 40 to interrupt therapy delivery. In some examples,processor 40 may issue such an instruction to stimulation generator 42in response to detecting a trigger event that causes processor 40 tocontrol stimulation generator 42 to generate and deliver the secondstimulation therapy.

In other examples, stimulation generator 42 delivers the firststimulation therapy to patient 12 in a closed loop manner. As describedbelow with respect to FIG. 8, in closed loop stimulation therapy,processor 40 controls stimulation generator 42 to deliver the firststimulation therapy to patient 12 based on at least one feedback, e.g.,a signal representative of a physiological response of patient 12 sensedby at least one of sensor 22 or a subset of electrodes 30, 32 of leads16, 18. For example, processor 40 may control stimulation generator 42to deliver the first stimulation therapy to patient 12 upon detecting abladder contraction frequency of patient 12 that is greater than orequal to a threshold bladder contraction frequency or a baselinecontraction frequency. Accordingly, the control of stimulation therapydelivery by processor 40 or stimulation generator 42 may includecontrolling a duration of the second time period during whichstimulation generator 42 does not deliver the first stimulation therapyto patient 12. In these examples, bladder data 52 can include a baselinecontraction frequency and/or a threshold contraction frequency forpatient 12.

In some examples, an inhibitory physiological response of patient 12 tothe first stimulation therapy may be observed during a post-stimulationperiod (also referred to herein as a second time period), in theseexamples, processor 40 can control stimulation generator 42 to deliverthe first stimulation therapy to patient 12 during a first time period(which can be predetermined) and cease delivering the first stimulationtherapy for a second time period. Processor 40 can then determine whento resume delivery of the first stimulation therapy, i.e., to restartthe first time period, by comparing a monitored bladder contractionfrequency to a threshold contraction frequency or a baseline contractionfrequency.

For example, when the bladder contraction frequency is one of equal tothe baseline contraction frequency, within a certain range of thebaseline contraction frequency, or is greater than or equal to thethreshold contraction frequency, processor 40 controls stimulationgenerator 42 to deliver the first stimulation therapy to patient 12. Asan example, processor 40 may compare the determined bladder contractionfrequency and the baseline contraction frequency to determine adifference between the determined contraction frequency and the baselinecontraction frequency. In some examples, when the difference is lessthan or equal to a specified value (e.g., a threshold difference value),processor 40 may control stimulation generator 42 to initiate deliveryof the first stimulation therapy to patient 12. In other words,processor 40 may end the second time period and initiate the first timeperiod based on the difference between the determined contractionfrequency and the baseline contraction frequency.

In some examples, bladder data 52 stores parameters with which processor40 detects a bladder contraction of patient 12 based on a sensedphysiological parameter, which can be sensed via sensor 22 or anothersensor (e.g., a sensing module of IMD 14). In some examples, processor40 monitors impedance of a bladder of patient 12 to detect a bladdercontraction. An example of a therapy system that is configured todetermine an impedance of a bladder of patient 12 is described withrespect to FIG. 16. Thus, bladder data 52 can include a thresholdimpedance value that is indicative of the bladder contraction. Processor40 may, for example, determine an impedance of the bladder and comparethe determined impedance value to a threshold impedance value stored inmemory 44 as bladder data 52. When the determined impedance value isless than the threshold impedance value stored in bladder data 52,processor 40 detects a bladder contraction. Processor 40 can determine abladder contraction frequency by, for example, monitoring impedance ofthe bladder for a predetermined duration of time to detect bladdercontractions, and determining a number of bladder contractions in thepredetermined duration of time.

In other examples, sensor 22 may be a pressure sensor and processor 40may detect bladder contractions based on changes in bladder pressureindicated by the pressure sensor. Thus, in some examples, bladder data52 includes a pressure value or a pressure change that is indicative ofa bladder contraction. Processor 40 may determine a pressure value basedon signals received from sensor 22 and compare the determined pressurevalue to a threshold value stored in bladder data 52 to determinewhether the signal is indicative of a bladder contraction. Processor 40can monitor bladder pressure to detect bladder contractions for apredetermined duration of time, and determine a bladder contractionfrequency by determining a number of contractions of bladder in thepredetermined time period.

In some cases, sensor 22 may be an EMG sensor, and processor 40 candetect bladder contractions based on an EMG of a muscle that is beingmonitored. The muscle is selected to be a muscle that is activated(e.g., contracts) when the patient's bladder contracts, and can be, forexample, a bladder wall, a detrusor muscle, or a urinary sphinctermuscle. Thus, in some examples, bladder data 52 includes an EMG templateor a threshold signal characteristic value (e.g., an amplitude value)that is indicative of a bladder contraction. Processor 40 may compare acharacteristic of a sensed EMG signal or the signal waveform itself tothe threshold signal characteristic value or EMG template stored inbladder data 52 to determine whether the signal is indicative of acontraction of bladder.

In examples in which stimulation generator 42 generates and delivers thefirst stimulation therapy in a closed loop manner, bladder data 52stores at least one parameter for controlling the closed loop therapydelivery. As discussed above, example parameters include a thresholdcontraction frequency and a baseline contraction frequency. A baselinecontraction frequency may be bladder contraction frequency at a timeprior to delivery of stimulation therapy by stimulation generator 42.For example, the baseline bladder contraction frequency may bedetermined by processor 40 after implantation of IMD 14 in patient 12,but before stimulation generator 42 delivers any stimulation therapy topatient 12. In some examples, the baseline bladder contraction frequencymay represent the patient state when no therapeutic effects fromdelivery of stimulation by IMD 14 are present.

Processor 40 may determine the baseline bladder contraction frequencyutilizing signals representative of physiological parameters receivedfrom at least one of sensor 22 or by sensing module of IMD 14 (not shownin FIG. 3), which can sense a physiological parameter of patient 12 viaa subset of electrodes 30, 32 of leads 16, 18, respectively, or via adifferent set of electrodes. In some implementations, processor 40 may,automatically or under control of a user, determine the thresholdbladder contraction frequency based on a baseline bladder contractionfrequency. For example, the threshold contraction frequency can be apredetermined percentage of the baseline bladder contraction frequencyor a percentage of the baseline bladder contraction frequency input by auser via programmer 20. As one example, the threshold frequency may bebetween approximately 75% and approximately 100% of the baseline bladdercontraction frequency.

In other examples, the threshold bladder contraction frequency may notbe based on a baseline bladder contraction frequency of patient 12, andmay instead be based on clinical data collected from a plurality ofpatients. For example, the threshold contraction frequency may bedetermined based on an average bladder contraction frequency of aplurality of patients during a bladder filling time period, e.g., duringa time period in which the plurality patients are not experiencing avoluntary or involuntary voiding event. In any case, the thresholdcontraction frequency may be stored in bladder data 52, and, in someexamples, processor 40 may utilize the threshold contraction frequencywhen delivering stimulation therapy in a closed loop manner to patient12.

In other examples, instead of utilizing a threshold bladder contractionfrequency or a baseline bladder contraction frequency, processor 40 maycontrol closed-loop delivery of the first stimulation therapy based onan EMG template, EMG characteristics (e.g., an amplitude or frequencyvalue of an EMG), or bladder pressure value, which can each indicate abladder state in which delivery of the first stimulation therapy isdesirable. Thus, bladder data 52 can include an EMG template, EMGcharacteristics, or threshold bladder pressure value in some examples.The EMG template, EMG characteristics, and bladder pressure values canbe determined using any suitable technique. In some cases, processor 40may generate the EMG template or determine the threshold bladderpressure value based on received signals generated by sensor 22 afterimplantation of IMD 14, but before stimulation generator 42 delivers anystimulation therapy to patient 12. The stored pressure value, EMGtemplate or EMG characteristics with which processor 40 controls thedelivery of the first stimulation therapy can indicate a bladdercontraction intensity that is indicative of a patient condition in whichthe first stimulation therapy is desirable, e.g., to reduce the bladdercontraction frequency or otherwise reduce the possibility of anoccurrence of an involuntary voiding event.

In examples in which sensor 22 includes an EMG sensor, processor 40 maycompare an EMG collected during the second time period to an EMGtemplate stored as bladder data 52 to determine whether the contractionsof bladder are indicative of a predetermined characteristic which causesprocessor 40 to control stimulation generator 42 to initiate delivery ofthe first stimulation therapy. The predetermined characteristic may be afrequency of contractions of bladder, an amplitude of the signal(representative of intensity of contractions of bladder), or the like.For example, the EMG may indicate whether the bladder contractions ofpatient 12 have returned to a baseline contraction frequency or pattern,such that delivery of the first stimulation therapy is desirable.

Closed loop therapy may allow processor 40 and stimulation generator 42to deliver more efficacious therapy to patient 12 by timing the deliveryof stimulation to respond to a specific physiological state (e.g., aparticular bladder contraction frequency or bladder contractionintensity) of patient 12. For example, based on the determined bladdercontraction frequency, processor 40 may cause stimulation generator 42to initiate delivery of the first stimulation therapy to patient 12prior to the end of the second time period specified in the selected oneof therapy programs 50. In this manner, closed loop therapy may reduceor substantially eliminate an amount of time that a bladder contractionfrequency is at a baseline level (e.g., a level substantially similar tothe contraction frequency of bladder prior to delivery of anystimulation therapy). In examples in which delivery of the firststimulation therapy generates a delayed inhibitory physiologicalresponse, timing the delivery of the first stimulation therapy to occurprior to observation of the baseline bladder contraction frequency mayhelp provide sufficient time for the first stimulation therapy togenerate the desired inhibitory physiological response.

Stimulation generator 42 delivers the first stimulation therapy topatient 12, and upon detecting a trigger event, processor 40 controlsstimulation generator 42 to cease delivery of the first stimulationtherapy and deliver the second stimulation therapy to patient 12, whichincludes substantially simultaneous bilateral stimulation. As discussedabove with respect to FIG. 1, the trigger event can include, forexample, detection of a physiological condition indicative of anincreased possibility of an involuntary voiding event or an imminentinvoluntary voiding event, a time of day, expiration of a timer, and/orinput from the patient (or a patient caretaker).

In examples in which the trigger event is based on a physiologicalparameter of patient 12 sensed by sensor 22 (or another sensor), bladderdata 52 can store values for detecting the trigger event based on asignal generated by sensor 22. One example of a trigger event is abladder volume greater than or equal to a trigger event thresholdbladder volume. As a volume of the patient's bladder increases, so maythe possibility of an involuntary voiding event, such that at thethreshold bladder volume, delivery of the more acute therapy provided bythe second stimulation therapy may be desirable to provide efficacioustherapy to patient 12. A bladder volume can be determined based on, forexample, an impedance of a pathway through the bladder.

Another example of a trigger event is a bladder contraction frequency orintensity that is greater than or equal to a trigger event threshold. Arelatively high bladder contraction frequency or bladder contractionintensity can indicate an increased possibility of an involuntaryvoiding event. In some examples, the bladder contraction frequency orintensity increases as the patient's bladder volume increases. Bladderdata 52 can include the trigger event threshold, which processor 40 canlater reference to detect the trigger event. Any of the techniquesdescribed above can be used to determine bladder contraction frequencyor intensity. The trigger event threshold may be different than thatused to control closed loop delivery of the first stimulation therapy.With respect to bladder contraction frequency and bladder contractionintensity, the trigger event threshold for initiating the delivery ofthe second stimulation therapy is greater than the threshold used toinitiate the delivery of the first stimulation therapy (i.e., restartthe first time period). Because the second stimulation therapy is usedas a secondary therapy that supplements the first stimulation therapy,the thresholds for triggering the delivery of the second stimulationtherapy are higher, such that the second stimulation therapy is usedless often and only when the additional layer of therapy is desirable tohelp prevent the occurrence of an involuntary voiding event.

Another example of a trigger event is an activity or posture state. Inthis example, bladder data 52 can include the output of sensor 22 (oranother sensor) that is indicative of a patient activity level orpatient posture state associated with an increased probability of anoccurrence of an involuntary voiding event. Memory 44 may associatepatient posture states or activity levels with the second stimulationtherapy, such that when processor 40 detects a posture state or activitylevel associated with the second stimulation therapy, processor 40controls stimulation generator 42 to generate and deliver the secondstimulation therapy to patient 12.

Processor 40 can determine an activity level of patient 12 based on amotion sensor that generates a signal that changes as a function ofpatient activity level using any suitable technique. For example,processor 40 may determine an activity level of patient 12 by samplingthe signal from the motion sensor (e.g., sensor 22 in some examples) anddetermine a number of activity counts during a sample period, where aplurality of activity levels are associated with respective activitycounts. In one example, processor 40 compares the signal generated bythe motion sensor to one or more amplitude thresholds stored withinmemory 44, and identifies each threshold crossing as an activity count.Processor 40 may determine a patient posture state based on a signalfrom the motion sensor using any suitable technique. In one example, aposture state may be defined as a three-dimensional space (e.g., aposture cone or toroid), and whenever a posture state parameter value,e.g., a vector from a three-axis accelerometer of the motion sensorresides within a predefined space, processor 40 indicates that patient12 is in the posture state associated with the predefined space.

In examples in which processor 40 controls the delivery of the secondstimulation therapy based on a time of day, bladder data 52 can storethe one or more times of day at which processor 40 initiates thedelivery of the second stimulation therapy. Processor 40 can include aclock that tracks the time of day.

in examples in which a timer is used to control the timing of thedelivery of the second stimulation therapy, bladder data 52 can storethe duration of the timer. As discussed above with respect to FIG. 1, insome examples, the duration of the tinier is based on the bladder fillcycle of patient 12. In some examples, processor 40 selects the durationof the timer and stores it as bladder data 52, or a clinician can selectthe duration of the timer and transmit the duration to IMD 14 (e.g., viaprogrammer 20) for storage as bladder data 52.

Other trigger events, such as other the trigger events that indicate aphysiological condition indicative of an increased possibility of aninvoluntary voiding event or an imminent involuntary voiding event, arecontemplated. Moreover, any of the trigger events described herein canbe used in any suitable combination to initiate the delivery of thesecond stimulation therapy.

The threshold values (also referred to as threshold levels) or templates(e.g., indicating a signal indicative of an imminent voiding event)stored in memory 44 as bladder data 52 may be determined using anysuitable technique. In some examples, the threshold values may bedetermined during implantation of IMD 14 or during a trial period in aclinician's office following implant of IMD 14. The trigger eventthreshold values, times of day, or timer durations may be adapted overtime based on user input, e.g., via external programmer 20. As anexample, patient 12 may indicate, via programmer 20, when an involuntaryvoiding event takes place. When the patient input is received, processor40 may determine a bladder impedance value during the event orimmediately prior to the event based in signals received from sensor 22.A new trigger event threshold value may be determined using thisimpedance value. As another example, the trigger event threshold valuestored as bladder data 52 may based on a running average of bladderimpedance values measured during involuntary voiding events.

in some examples, stimulation generator 42 delivers the secondstimulation therapy for a predetermined therapy period, the duration ofwhich may be stored in memory 44 and/or a memory of another device(e.g., programmer 20). The therapy period may be, for example,approximately 10 seconds to approximately 60 seconds, although othertherapy periods are contemplated. The predetermined period of time canbe determined by a clinician in some examples and stored in memory 44 ofIMD.

In some examples, in addition to or instead of the predetermined therapyperiod, stimulation generator 42 delivers the second stimulation therapyfor a therapy period controlled by patient 12. In such examples, patient12 may interact with programmer 20 to control the delivery time. As anexample, stimulation generator 42 may deliver the second stimulationtherapy as long as patient 12 presses a button on a keypad or touchscreen of programmer 20. As another example, processor 40 controlsstimulation generator 42 to initiate the delivery of the secondstimulation therapy upon receiving a first input from patient 12 (e.g.,by presses a button on a keypad or touch screen of programmer 20) andcontrols stimulation generator 42 to terminate the delivery of thesecond stimulation therapy upon receiving a second subsequent input frompatient 12 indicating the second stimulation therapy should beterminated. In operation, processor 40 can receive the patient input viatelemetry module 46 and control stimulation generator 42 to delivertherapy according to the received input.

If processor 40 controls the duration of the therapy period of thesecond stimulation therapy based on both a predetermined period of timeand the patient input, processor 40 can, for example, controlstimulation generator 42 to deliver the second stimulation therapy forthe longer of the predetermined period of time or the period of timedetermined based on patient input, or, in other examples, the shorter ofthose two periods of time.

In other examples, processor 40 controls the duration of the therapyperiod during which stimulation generator 42 delivers the secondstimulation therapy based on a physiological condition of patient 12.For example, in examples in which stimulation generator 42 initiates thedelivery of the second stimulation therapy based on a sensed patientcondition, stimulation generator 42 delivers the second stimulationtherapy until the condition is no longer detected. As an example,processor 40 can control stimulation generator 42 to initiate thedelivery of the second stimulation therapy in response to detecting abladder impedance less than or equal to a predetermined trigger eventthreshold and continue delivering the second stimulation therapy untilthe bladder impedance is greater than the predetermined trigger eventthreshold. This threshold may be different than that used to detect abladder contraction. When processor 40 detects a bladder impedance thatis greater than the predetermined termination threshold, processor 40may determine that the volume of the patient's bladder has decreased(e.g., due to voluntary voiding by patient 12), such that termination ofthe second stimulation therapy is appropriate. In the foregoing example,stimulation generator 42 delivers the second stimulation therapy until arelatively low bladder fill level of patient 12 is detected.

A relatively low bladder level of patient 12 that causes stimulationgenerator 42 to terminate delivery of the second stimulation therapy canbe detected using other techniques. In some examples, as described withrespect to FIG. 6, processor 40 detects a relatively low bladder filllevel of patient 12 based on patient input that is provided afterpatient 12 voluntarily voids. Processor 40 can receive the input from aninput device separate from IMD 12 (e.g., programmer 20) via telemetrymodule 46 or from a sensor that is coupled to processor 40 (e.g., amotion sensor that detects tapping of IMD 14 by patient 12).

Telemetry module 46 includes any suitable hardware, firmware, softwareor any combination thereof for communicating with another device, suchas programmer 20 (FIG. 1). Generally, processor 40 controls telemetrymodule 46 to exchange information with medical device programmer 20and/or another device external to IMD 14. Under the control of processor40, telemetry module 46 may receive downlink telemetry, e.g., patientinput, from and send uplink telemetry, e.g., an alert, to programmer 20with the aid of an antenna, which may be internal and/or external.Processor 40 may provide the data to be uplinked to programmer 20 andthe control signals for the telemetry circuitry within telemetry module46, and receive data from telemetry module 46. Processor 40 may transmitoperational information and receive stimulation programs or stimulationparameter adjustments via telemetry module 46. Also, in some examples,IMD 14 may communicate with other implanted devices, such asstimulators, control devices, or sensors, via telemetry module 46.

Processor 40 monitors patient input received via telemetry module 46 andtakes appropriate action. As previously described, in some examples,telemetry module 46 may receive an indication from programmer 20 thatpatient 12 provided input indicative of an imminent voiding event or arequest for delivery of the second stimulation therapy. Upon receivingthe patient input via telemetry module 46, processor 40 may controlstimulation generator 42 to generate and deliver the second stimulationfor a predetermined amount of time or until a particular patientcondition is detected, to manually abort the second stimulation therapy,or inhibit the second stimulation therapy during voluntary voiding.

Telemetry module 46 can also receive patient input indicating avoluntary voiding event. In response to receiving the input, processor40 may suspend delivery of the second stimulation therapy, and, in someexamples, the first stimulation therapy, for a pre-determined period oftime, e.g., 2 minutes. During this time period, processor 40 may ignoresignals indicative of the patient parameter, such as signals generatedby sensor 22. Processor 40 may ignore these signals for a predeterminedperiod of time, such as approximately two minutes. After two minutes haselapse, processor 40 may resume the first stimulation therapy if thefirst stimulation therapy was suspended, and continue monitoring patient12 to detect trigger events. As discussed above, the input indicative ofthe voluntary voiding event can also be used to control the duration ofthe second stimulation therapy.

Power source 60 delivers operating power to the components of IMD 14.Power source 60 may include a battery and a power generation circuit toproduce the operating power. In some examples, the battery may berechargeable to allow extended operation.

FIG. 4 is a block diagram illustrating example components of externalprogrammer 20. While programmer 20 may generally be described as ahand-held computing device, the programmer may be a notebook computer, acell phone, or a workstation, for example. As illustrated in FIG. 4,external programmer 20 may include a processor 60, memory 62, userinterface 64, telemetry module 66, and power source 68. Memory 62 maystore program instructions that, when executed by processor 60, causeprocessor 60 and external programmer 20 to provide the functionalityascribed to external programmer 20 throughout this disclosure.

In general, programmer 20 comprises any suitable arrangement ofhardware, alone or in combination with software and/or firmware, toperform the techniques attributed to programmer 20, and processor 60,user interface 64, and telemetry module 66 of programmer 20. In variousexamples, programmer 20 may include one or more processors, such as oneor more microprocessors, DSPs, ASICs, FPGAs, or any other equivalentintegrated or discrete logic circuitry, as well as any combinations ofsuch components. Programmer 20 also, in various examples, may include amemory 62, such as RAM, ROM, PROM, EPROM, EEPROM, flash memory, a harddisk, a CD-ROM, a floppy disk, a cassette, magnetic media, or opticalmedia comprising executable instructions for causing the one or moreprocessors to perform the actions attributed to them. Moreover, althoughprocessor 60 and telemetry module 66 are described as separate modules,in some examples, processor 60 and telemetry module 66 are functionallyintegrated.

Memory 62 may store program instructions that, when executed byprocessor 60, cause processor 60 and programmer 20 to provide thefunctionality ascribed to programmer 20 throughout this disclosure. Insome examples, memory 62 may further include therapy information, e.g.,therapy programs defining the first stimulation therapy and secondstimulation therapy, similar to those programs 50 (FIG. 3) stored inmemory 44 of IMD 14, and bladder data similar to bladder data 52 storedby IMD 14. The stimulation programs and/or bladder data 42 stored inmemory 62 may be downloaded into memory 44 of IMD 14 or vice versa.

User interface 64 may include a button or keypad, lights, a speaker forvoice commands, a display, such as a LCD, LED, or CRT. In some examplesthe display may be a touch screen. As discussed in this disclosure,processor 60 may present and receive information relating to stimulationtherapy via user interface 64. For example, processor 60 may receivepatient input via user interface 64. The input may be, for example, inthe form of pressing a button on a keypad or selecting an icon from atouch screen.

Processor 60 may also present information to patient 12 (or a patientcaretaker) in the form of alerts related to delivery of the stimulationtherapy to patient 12 via user interface 64. Telemetry module 66supports wireless communication between IMD 14 and programmer 20 underthe control of processor 60. Telemetry module 66 may also be configuredto communicate with another computing device via wireless communicationtechniques, or direct communication through a wired connection.Telemetry module 66 may be substantially similar to telemetry module 46described above, providing wireless communication via an RF or proximalinductive medium. In some examples, telemetry module 66 may include anantenna, which may take on a variety of forms, such as an internal orexternal antenna. Examples of local wireless communication techniquesthat may be employed to facilitate communication between programmer 20and another computing device include RF communication according to the802.11 or Bluetooth specification sets, infrared communication, e.g.,according to the IrDA standard, or other standard or proprietarytelemetry protocols. In this manner, other external devices may becapable of communicating with programmer 20 without needing to establisha secure wireless connection.

An external antenna that is coupled to programmer 20 may correspond to aprogramming head that may be placed over IMD 14. Although not shown,programmer 20 may additionally or alternatively include a data ornetwork interface to another computing device, to facilitatecommunication with the other device, and presentation of informationrelating to first and second stimulation therapies via the other device.

IMD 14 and/or programmer 20 may control of the timing of the delivery ofthe first stimulation therapy and the second stimulation therapy thatgenerate one or more physiological responses to manage bladderdysfunction of patient 12. If external programmer 20 controls thestimulation, programmer 20 may transmit therapy programs forimplementation by processor 40 to IMD 14. Alternatively, programmer 20may transmit a signal to IMD 14 indicating that processor 40 shouldexecute locally stored programs or therapy routines. In such a manner,control over the electrical stimulation may be distributed between IMD14 and external programmer 20, or may reside in either one alone.

In one example, patient 12 may control the second stimulation therapydelivered by IMD 14 via programmer 20. For example, patient 12 mayinitiate and/or terminate delivery of the second stimulation therapy byIMD 14 via user interface 64. In this way, patient 12 may use programmer20 to deliver the second stimulation therapy “on demand,” such as whenpatient 12 senses the onset of a leakage episode or undertakes anactivity in which an additional measure of therapy to help prevent theoccurrence of an involuntary voiding event is desirable.

In some examples, patient 12 may indicate an intent to void via userinterface 64, and processor 60 may implement a blanking interval throughcommunication of the indication to IMD 14 via telemetry module 66. Forexample, processor 60 may transmit a command signal to IMD 14 thatindicates processor 40 of IMD 14 should temporarily suspend delivery ofthe second stimulation therapy or both the first and second stimulationtherapies so that the stimulation does not interfere with the patient'sability to void. In some examples, patient 12 can indicate the length oftime for a voiding event by pressing and holding down a button of userinterface 64 for the duration of a voiding event, pressing a button afirst time to initiate voiding and a second time when voiding iscomplete. In other times, programmer 20 or IMD 14 automaticallydeterminates a duration of a voiding event based on a predeterminedperiod of time following the indication of voluntary voiding provided bypatient 12. In each case, programmer 20 causes IMD 14 to temporarilysuspend the relevant stimulation therapy so that voluntary voiding ispossible.

In examples in which patient 12 provides input, via user interface 64,indicative of the completion of a voluntary voiding event, processor 60may transmit a signal to processor 40 of IMD 14 via the respectivetelemetry modules 66, 46. Processor 40 of IMD 14 may then, as describedabove, control the duration of the second stimulation therapy to patient12 based on this input, such as by terminating the delivery of thesecond stimulation therapy upon receiving the input indicative of thecompletion of a voluntary voiding event.

Power source 68 delivers operating power to the components of programmer20. Power source 68 may include a battery and a power generation circuitto produce the operating power. In some examples, the battery may berechargeable to allow extended operation.

FIG. 5 is a flow diagram illustrating an example technique implementedby a therapy system, such as therapy system 10 (FIG. 1), to reduce thelikelihood of incontinence events. While FIGS. 5-8 are described withrespect to therapy system 10, in other examples, the techniques for thefirst and second stimulation therapies described herein may beimplemented by other therapy systems, which may include differentcomponents or configurations than therapy system 10. In addition, whileprocessor 40 is primarily referred to in FIGS. 5-8, in other examples, aprocessor of another device (e.g., programmer 20), alone or incombination with processor 40, can perform the techniques shown in FIGS.5-8.

In the technique shown in FIG. 5, under control of processor 40,stimulation generator 42 of IMD 14 delivers the first stimulationtherapy to patient 12 (70). In some examples, processor 40 initiates thedelivery of the first stimulation therapy by stimulation generator 42upon activation of chronic therapy delivery by the clinician.Stimulation generator 42 delivers stimulation to target tissue sites onrespective lateral sides of patient 12 at different times (e.g., in atime interleaved manner). In some examples, the target tissues are eachproximate at least one of a spinal nerve, a sacral nerve, a pudendalnerve, dorsal genital nerve, a tibial nerve, an inferior rectal nerve, aperineal nerve, or a branch thereof on the respective lateral side ofpatient 12.

In one example, stimulation generator 42 delivers the first stimulationby delivering substantially balanced bilateral stimulation to patient12, whereby the stimulation delivered to a first target tissue site on afirst lateral side of patient 12 is substantially similar in intensityand/or duration as the stimulation delivered to a second target tissuesite on a second lateral side of patient 12. In other examples, for thefirst stimulation therapy, the stimulation delivered to the two lateralsides of patient 12 is imbalanced, e.g., due to different stimulationintensities and/or stimulation periods in which IMD 14 is activelydelivering stimulation to patient 12.

Processor 40 controls stimulation generator 42 to generate and deliverthe first stimulation therapy to patient 12 in an open loop manner, or,as discussed in further detail with respect to FIG. 8, in a closed loopmanner. In either example, the first stimulation therapy can beconfigured to provide an immediate inhibition of a physiologicalresponse related to voiding (e.g., a reduction in bladder contractionfrequency) or a more delayed response, in which the physiologicalresponse is not observed until after stimulation generator 42 deliversstimulation to patient 12.

Processor 40 determines whether a trigger event is detected (72).Examples of trigger events that may be detected include, but are notlimited to, bladder contraction or intensity level exceeding (e.g.,greater than or equal to) a trigger event threshold level, abnormaldetrusor muscle activities (e.g., as indicated by an EMG), patientactivity level exceeding a threshold level, a particular patient posturestate or activity level, a time of day, expiration of a timer, andpatient input. As previously described, processor 40 may monitor bladderimpedance, bladder pressure, pudendal or sacral afferent nerve signals,a urinary sphincter EMG, or any combination thereof to detect changes inbladder contraction and/or intensity level. These physiologicalparameters may be sensed by, for example, sensor 22 or another sensor(e.g., a sensing module that is a part of IMD 14).

The steps of delivering the first stimulation therapy and detecting arigger event are illustrated in FIG. 5 as being sequential, but itshould be understood that these steps may be performed simultaneouslyinstead of sequentially. For example, processor 40 can detect thetrigger event while the first stimulation therapy is being delivered topatient 12.

If processor 40 does not detect a trigger event after initiatingdelivery of the first stimulation therapy (“NO” branch of block 72),stimulation generator 42 continues to deliver the first stimulationtherapy (70) without delivering the second stimulation (70). On theother hand, if processor 40 detects a trigger event after initiatingdelivery of the first stimulation therapy (“YES” branch of block 72),processor 40 controls stimulation generator 42 to deliver the secondstimulation therapy by at least delivering stimulation substantiallysimultaneously to both lateral sides of patient 12 (74). As previouslydescribed, the second stimulation therapy is selected to have adifferent physiological effect on patient 12 than the first stimulationtherapy, such as a more immediate decrease in bladder contractionfrequency or a more drastic decrease e.g., greater decrease) in bladdercontraction frequency. In the example shown in FIG. 5, the first andsecond stimulation therapies are delivered at different times. Thesubstantially simultaneous bilateral stimulation can be substantiallybalanced between the lateral sides of patient 12 in some examples andcan be imbalanced in other examples.

In one example, the trigger event is a bladder fill level at or above athreshold fill level. The trigger event can be detected, for example,when processor 40 detects a bladder impedance value that is less than atrigger event threshold impedance value stored in memory 44 as bladderdata 52 (FIG. 3). Other techniques for determining a bladder fill levelare contemplated, such as based on a strain gauge sensor (which can be,for example, sensor 22) on a bladder surface. In another example, thetrigger event is a bladder contraction frequency greater than or equalto a trigger even threshold value. Any suitable technique, such as thosedescribed above, can be used to detect a bladder contraction. In anotherexample, the trigger event is a bladder contraction intensity greaterthan or equal to a trigger even threshold value. The bladder contractionintensity can be determined using any suitable technique, such as, butnot limited to, a pressure value sensed by sensor 22. In anotherexample, the trigger event is a predetermined patient posture state oractivity level, which can be stored in memory 44 (FIG. 3) of IMD 14 ormemory of another device.

In addition to or instead of the trigger events that are based on asensed patient parameter, the trigger event can be patient input.Patient 12 may provide the patient input via user interface 64 ofprogrammer 20, e.g., by activating a button on a keypad or select anicon using a touch screen of programmer 20. Programmer 20 wirelesslycommunicates the patient input to IMD 14 via the respective telemetrymodules 66, 46. In other examples, patient 12 may provide inputindicating the delivery of the second stimulation therapy is desirableby directly interacting with IMD 14. For example, IMD 14 may include amotion sensor that detects movement of IMD 14 and patient 12 may provideinput by tapping the skin proximate IMD 14 in a predetermined pattern,such that processor 40 detects the movement and characterizes themovement as patient input.

In another example, the trigger event is an expiration of a timer thatprocessor 40 starts upon receiving an indication that patient 12 hasvoluntarily voided, thereby reducing the bladder fill level or evenemptying the bladder. The duration of the timer can be, for example,selected to be a duration of time that is expected to pass before thebladder of patient 12 is filled to a level that increases thepossibility of an involuntary voiding event. Thus, at the expiration ofthe timer, the bladder of patient 12 is at a volume for which anadditional layer of therapy provided by the second stimulation therapyis desirable to help prevent the occurrence of an involuntary voidingevent. Processor 40 can receive an indication that patient 12 hasvoluntarily voided using any suitable technique, e.g., receiving inputfrom patient 12 (or a patient caretaker) via programmer 20 or bydirectly interacting with IMD 14 or based on a physiological parametersensed by IMD 14 or sensor 22 that indicates a bladder volume.

In some examples, stimulation generator 42 delivers the secondstimulation therapy (74) for a therapy period duration controlled bypatient 12. For example, patient 12 may control the duration of thetherapy period for the second stimulation therapy by interacting withprogrammer 20, e.g., by pressing a button on a keypad or a touch screento terminate the second stimulation therapy or set a duration of timefor the second stimulation therapy, or by interacting directly with IMD14 (e.g., by tapping skin superior to the implanted IMD 14). IMD 14 canbe programmed with a maximum duration for the second stimulationtherapy, such that patient 12 is provided with limited control of theduration of the second stimulation therapy. The maximum duration for thesecond stimulation therapy can be, for example, approximately 3 minutes,although other durations of time are contemplated.

In addition to or instead of determining the therapy period durationbased on patient input, stimulation generator 42 can deliver the secondstimulation therapy (74) for a predetermined period of time, e.g., about10 seconds to about 50 seconds, immediately following the detection ofthe trigger event. The duration of the predetermined period of time maybe selected such that an imminent involuntary voiding event issuppressed. After the predetermined period of time, processor 40controls stimulation generator 42 to resume delivery of the firststimulation therapy (70), unless some intervening input is received thatcauses stimulation generator 42 to suspend delivery of stimulationtherapy to patient 12.

After terminating the delivery of the second stimulation therapy topatient 12, stimulation generator 42 continues to deliver the firststimulation therapy (70) and the technique shown in FIG. 5 is repeatedas necessary. Thus, IMD 14 delivers the first stimulation therapy and,when triggered, delivers the second stimulation therapy for a limitedduration of time (e.g., shorter in duration than the duration of timethat the first stimulation therapy is delivered).

FIG. 6 is a flow diagram of another technique with which processor 40can control stimulation generator 42 to generate and deliver the firstand second stimulation therapies. As shown in the flow diagram of FIG.6, after stimulation generator 42 delivers the second stimulationtherapy for a predetermined period of time, processor 40 can determinewhether the trigger event is still present (75) using any of thetechniques described above with respect to FIG. 5. For example, if thetrigger event is the detection of a particular patient condition,processor 40 can determine whether the patient condition that triggeredthe delivery of the second stimulation therapy is still observed. As anexample, processor 40 may determine whether the bladder contractions arestill greater than or equal to a trigger event threshold value. Asanother example, if the trigger event is patient input, processor 40 candetermine whether the patient has provided additional input thatindicates delivery of the second stimulation therapy is desirable.

If the trigger event is still detected after the delivery of the secondstimulation therapy (“YES” branch of block 75), processor 40 may controlstimulation generator 42 to deliver the second stimulation therapy (74)again for another predetermined period of time. This technique may berepeated in some examples until the trigger event is no longer detected.If the trigger event is not detected after delivery of the secondstimulation therapy for a predetermined duration of time (“NO” branch ofblock 75), processor 40 can cease delivery of the second stimulationtherapy and resume delivery of the first stimulation therapy (74). Inother examples, processor 40 can cease delivery of the secondstimulation therapy and resume the first stimulation therapy when afeedback indicates the first stimulation therapy is desirable, e.g., thefirst stimulation therapy can be controlled in a closed loop manner. Aclosed loop technique with which processor 40 may control the firststimulation therapy is described with respect to FIG. 8.

FIG. 7 is a flow diagram of another technique with which processor 40can control stimulation generator 42 to generate and deliver the firstand second stimulation therapies. In the technique shown in FIG. 7,stimulation generator 42 delivers the second stimulation therapy topatient 12 for a therapy period that has a duration that is based onvoiding by patient 12. The technique shown in FIG. 7 is performed in aclosed loop manner.

To initiate of the delivery of therapy to patient 12, processor 40detects a voiding event (“YES” branch of block 76), in which patient 12voids and decreases the fill level of the bladder. The voiding event isvoluntary in the example shown in FIG. 7 examples. Processor 40 candetect voiding by patient 12 using any suitable technique. In someexamples, processor 40 receives input from patient 12 (or a patientcaretaker) indicating the occurrence of a voluntary voiding event.Patient 12 can provide input to programmer 20 or another externaldevice, which may then transmit an indication of the input to processor40, or patient 12 may interact directly with IMD 14 (e.g., by tappingskin superior to the implant site of IMD 14).

In other examples, processor 40 detects an occurrence of a voiding eventbased on a sensed physiological parameter of patient 12. For example,processor 40 can detect the occurrence of a voluntary voiding eventbased on an EMG of the urinary sphincter muscle of patient 12 or anothermuscle that activates during voiding. Sensor 22 (FIG. 1) may generatethe EMG in some examples, or processor 40 may sense the EMG of themuscle via a subset of electrodes 30, 32 of leads 16, 18 (FIG. 3). Insome examples, memory 44 of IMD 14 (FIG. 3) stores an EMG template orthreshold values (e.g., a signal amplitude or frequency value) that isassociated with a voluntary voiding event, and processor 40 compares asensed EMG to the stored template or threshold to detect the voluntaryvoiding event. For example, when a sensed EMG substantially matches thestored template, processor 40 may determine that patient 12 ispurposefully activating the monitored muscle to voluntarily void. Avoluntary voiding event can also be detected based on otherphysiological parameters, such as a bladder pressure, urinary sphincterpressure, and the like. In addition, other techniques for detecting avoluntary voiding event may be used. Similar techniques can be used todetect an involuntary voiding event and processor 40 can be configuredto distinguish between voluntary and involuntary voiding events.

After detecting a voluntary voiding event, processor 40 controlsstimulation generator 42 to deliver the first stimulation therapy (70)and starts a timer (77). As discussed above, the duration of the timeris predetermined and stored in memory 44 of IMD 14 and/or a memory ofanother device. The timer duration may be based on a bladder fill cycleof patient 12. As shown in FIG. 7, stimulation generator 42 continues todeliver the first stimulation therapy to patient 12 until the timerexpires. Upon expiration of the timer (“YES” branch of block 78),processor 40 controls stimulation generator 42 to terminate delivery ofthe first stimulation therapy and deliver the second stimulation therapyto patient 12 (74). In the example shown in FIG. 7, processor 40delivers the second stimulation therapy to patient 12 until a voluntaryvoiding event is detected (“NO” branch of block 76). When the voluntaryvoiding event is detected, processor 40 may terminate the delivery ofthe second stimulation therapy, and, in some cases, resume the firststimulation therapy at that time, or at a later time, such as when apatient condition indicative of a desirability for the first stimulationtherapy is detected.

The technique shown in FIG. 7 adapts the timing of the secondstimulation therapy to the bladder fill cycle of patient 12. A bladderfill cycle begins immediately after the patient voluntarily voids. Astime passes since the patient's last voluntary voiding event, thepatient's bladder fills, such that the possibility of the occurrence ofan involuntary voiding event may be increase through the bladder fillcycle because, at least with some patients, the bladder contractionfrequency may increase as the fill level of the patient's bladderincreases. In this way, the second stimulation therapy, which mayprovide a greater inhibitory physiological response that reduces thebladder contraction frequency of patient 12 compared to the firststimulation therapy, may be more desirable as the bladder fill cycle ofpatient 12 progresses, e.g., some period of time after a voluntaryvoiding event of patient 12.

Upon detecting a voluntary voiding event (“YES” branch of block 76),processor 40 may terminate the delivery of the second stimulationtherapy and initiate the delivery of the first stimulation therapy (70),thereby restarting the therapy cycle shown in FIG. 7. In examples inwhich the first stimulation therapy is delivered according to a therapycycle that includes a first time period in which stimulation isdelivered to patient 12 and a second time period in which no stimulationis delivered to patient 12, processor 40 can initiate the delivery ofthe first stimulation therapy in the first time period or the secondtime period. For example, processor 40 can terminate the delivery of thesecond stimulation therapy and deliver electrical stimulation to patientuntil a patient condition for which the first stimulation therapy isdesirable is detected, e.g., using the technique shown in FIG. 8.

After patient 12 voluntarily voids, the bladder fill cycle of patient 12restarts, such that the possibility of the occurrence of an involuntaryvoiding event is reduced, thereby meriting delivery of the firststimulation therapy, which provides a less intense inhibitoryphysiological response. As discussed above, patient 12 may exhibit arelatively tow bladder contraction frequency at the beginning of thebladder fill cycle that may gradually increase throughout the bladderfill cycle.

Using the techniques shown in FIGS. 5-7, IMD 14 can provide responsivestimulation to patient 12 to manage bladder dysfunction. Delivering thesecond stimulation therapy upon detection of a trigger event, ratherthan on a substantially regular basis, may help reduce muscle fatigue bylimiting the amount of the second stimulation therapy, which has ahigher intensity than the first stimulation therapy. In addition,implementing the second stimulation therapy only when needed may helpconserve power of power source 48 (FIG. 3) of IMD 14. Conserving powermay help elongate the useful life of IMD 14.

FIG. 8 is a flow diagram illustrating an example technique fordelivering the first stimulation therapy in a closed loop manner. Thetherapy cycle for the closed loop therapy shown in FIG. 8 includes afirst time period during which stimulation generator 42 deliversstimulation to patient 12 and a second time period during whichstimulation generator 42 does not deliver stimulation to patient 12. Inthe example illustrated in FIG. 8, the duration of the second timeperiod may be adjusted by processor 40 in response to an input receivedfrom sensor 22 or another sensor. In other examples, the duration of thesecond time period may be adjusted in response to another input, e.g.,from a user such as patient 12 or a clinician or another sensing moduleof therapy system 10. In some examples, in addition to or as analternative to adjusting the duration of the second time period, theduration of the first time period may be adjusted based on an inputreceived by processor 40.

Processor 40 controls stimulation generator 42 to deliver the firststimulation therapy to patient 12 via a subset of electrodes 30, 32,where the stimulation is defined by a therapy program (80). As describedabove, the first stimulation therapy delivered during the first timeperiod according to the therapy program may elicit substantially noinhibitory physiological response related to voiding in patient 12during the first time period, or may elicit a first inhibitoryphysiological response related to voiding in patient 12 during the firsttime period. In some examples, the first inhibitory physiologicalresponse related to voiding includes a reduction in bladder contractionfrequency.

At the end of the first time period, processor 40 controls stimulationgenerator 42 to cease delivering stimulation (82) and detects a signalindicative of a physiological response of patient 12 to the stimulationdelivery according to the therapy program during the first time period(84). In the example shown in FIG. 8, the physiological response isdetermined based on a bladder contraction frequency of patient 12. Inthe example shown in FIG. 8, processor 40 compares the bladdercontraction frequency, to a threshold value, such as contractionfrequency or a baseline contraction frequency (86). When processor 40determines that the bladder contraction frequency of patient 12 is abovethe threshold value or within a predetermined amount of the baselinecontraction frequency (“YES” branch of block 86), processor 40 controlsstimulation generator 42 to initiate delivery of the first stimulationto patient 12 (80). This restarts the first period of time of thetherapy cycle. However, when processor 40 determines that the bladdercontraction frequency of bladder of patient 12 is below the thresholdvalue or within a predetermined amount of the baseline contractionfrequency (“NO” branch of block 86), processor 40 may continue to detectthe signal representing the physiological response (84) until thebladder contraction frequency of interest is detected.

The steps of delivering the first stimulation therapy and monitoringpatient 12 to detect contractions of bladder are illustrated in FIG. 8as being sequential, but it should be understood that these steps may beperformed simultaneously instead of sequentially. For example, processor40 may detects a signal representing a physiological response (84) whilecontrolling stimulation generator 42 to deliver the first stimulationtherapy (80) and after controlling stimulation generator 42 to ceasedelivery of the first stimulation therapy (82).

FIGS. 9A-9C are schematic illustrations of stimulation signals deliveredto the first and second lateral sides of patient 12 during the firstelectrical stimulation therapy. The first and second lateral sides canbe, for example, the left and right sides of patient 12, where the leftand right sides are demarcated by spinal cord 24 in FIG. 1. While FIGS.9A-9C, as well as FIGS. 10A-10F, illustrate stimulation pulses, in otherexamples, IMD 14 may generate and deliver continuous time signals.Substantially similar stimulation regimes as those shown in FIGS. 9A-10Fcan be adapted for use with continuous time signals.

In the examples shown in FIGS. 9A-9C, when stimulation generator 42 ofIMD 14 delivers stimulation signals to the first and second lateralsides of patient 12 at different times, the stimulation signals do notoverlap in time. FIG. 9A illustrates a stimulation pulse regime in whichIMD 14 delivers the first stimulation therapy to patient 12 bydelivering stimulation pulses to the first and second lateral sides ofpatient 12 in an alternating fashion (e.g., a time interleaved manner).In the example pulse regime shown in FIG. 9A, each stimulation pulse 88has substantially the same pulse width and amplitude, such that thefirst and second lateral sides of patient 12 receive substantiallysimilar intensities of stimulation. In this way, FIG. 9A illustrates asubstantially balanced bilateral stimulation therapy in which the firstand second lateral sides of patient 12 receive stimulation signals inalternating time slots.

As shown in FIG. 9A, IMD 14 delivers a first pulse train 87A to a firstlateral side of patient 12 during a first stimulation period 89A, wherepulse train 87A includes a plurality of electrical stimulation pulses88. After first stimulation period 89A, IMD 14 stops delivery ofstimulation to the first lateral side of patient 12 and initiatesdelivery of second pulse train 87B to a second lateral side of patient12 during a second stimulation period 89B. Second pulse train 87B alsoincludes a plurality of pulses 88. Second stimulation period 89Bimmediately follows first stimulation period 89A. Although not shown inFIG. 9A, after second stimulation period 89B, IMD 14 may stop deliveryof stimulation to the second lateral side of patient 12 and initiatedelivery of another pulse train 87A for a third stimulation period thatis equal in duration to first stimulation period 87A. Thereafter, IMD 14may deliver pulse train 87B to second lateral side of patient 12 for astimulation period equal to stimulation period 89B, and so on and soforth. This alternating delivery of stimulation to the lateral sides ofpatient 12 may continue as long as desired.

As shown in FIG. 9A, during first stimulation period 89A, IMD 14 doesnot deliver electrical stimulation to the second lateral side of patient12, and during second stimulation period 89B, IMD 14 does not deliverelectrical stimulation to the first lateral side of patient 12. Asdiscussed in further detail below, stimulation periods 89A, 89B may besubstantially equal (e.g., equal or nearly equal) in some examples, andmay be different in other examples. In addition, pulse trains 87A, 88Amay be substantially equal number of pulses 88 (e.g., equal or nearlyequal) in some examples, and may have a different number of pulses inother examples.

FIG. 9B illustrates an example of an imbalanced first stimulationtherapy in which the first and second lateral sides of patient 12receive different stimulation pulses, and in which the stimulationperiods and pulse train lengths differ for each lateral side. IMD 14also delivers stimulation pulses to the first and second lateral sidesof patient 12 in an alternating fashion in the example shown in FIG. 9B.In particular, IMD 14 delivers pulse train 91A including a plurality ofstimulation pulses 90 to a first side of patient 12 during firststimulation period 93A, and, after the end of first stimulation period93A, IMD 14 stops delivery of stimulation to the first lateral side ofpatient 12 and initiates delivery of second pulse train 91B including aplurality of stimulation pulses 92 to a second lateral side of patient12 during second stimulation period 93B. Second stimulation period 93Bdoes not overlap with first stimulation period 93A. Although not shownin FIG. 9B, after second stimulation period 939, IMD 14 may stopdelivery of stimulation to the second lateral side of patient 12 andinitiate delivery of another pulse train 91A for a third stimulationperiod that is equal in duration to first stimulation period 93A. Thisalternating delivery of stimulation to the lateral sides of patient 12may continue as long as desired.

Stimulation pulses 90, 92 have substantially similar amplitudes, buthave different pulse widths. In other examples, stimulation pulsesdelivered to different lateral sides of patient 12 may havesubstantially similar pulse widths, but different pulse amplitudes. Dueto the different stimulation pulses 90, 92, different pulse train 91A,91B, and different stimulation periods 93A, 93B, the first and secondlateral sides of patient 12 receive different intensities ofstimulation, such that the bilateral stimulation therapy shown in FIG.9B is imbalanced. In other examples, imbalanced stimulation firststimulation therapy may be achieved using other techniques, such as withsimilar stimulation period durations, but different pulse trains.

FIG. 9C illustrates another example of an imbalanced first stimulationtherapy. IMD 14 delivers stimulation pulses 94 to the first and secondlateral sides of patient 12 at different times in the example shown inFIG. 9C. While each stimulation pulse 94 delivered to the lateral sidesof patient 12 is substantially similar, the imbalance in the stimulationdelivered to the first and second lateral sides of patient 12 shown inFIG. 9C is achieved by delivering stimulation to the first lateral sideof patient 12 for a longer duration of time than the second lateral sideof patient 12. In particular, in the example shown in FIG. 9C, IMD 14delivers pulse train 95A including four stimulation pulses 94 to thefirst lateral side of patient 12 during stimulation period 96A, and,after the end of stimulation period 96A, IMD 14 stops deliveringstimulation to the first lateral side of patient and initiates deliveryof second pulse train 95B to the second lateral side of patient 12during second stimulation period 96B. Second pulse train 95B includesthree stimulation pulses 94. As shown in FIG. 9C, during secondstimulation period, IMD 14 As shown in FIG. 13C, at the beginning ofsecond stimulation period, due to the configuration of pulse train 95B,IMD 14 does not immediately deliver a pulse 94, but waits a period oftime (e.g., equal to the difference in time between the end of one pulse124 and the beginning of another pulse 94 in pulse train 95B) prior todelivering a pulse 94. In other examples, IMD 14 immediately delivers apulse 94 at the beginning of second stimulation period 95B.

In other examples, stimulation pulses delivered to the first lateralside of patient 12 may have a longer pulse width than the stimulationpulses delivered to the second lateral side of patient 12, or adifferent amplitude.

Stimulation periods 96A, 96B are substantially equal in the exampleshown in FIG. 9C, such that IMD 14 actively delivers stimulation to thefirst and second lateral sides of patient 12 for the same durations oftime (though at different, non-overlapping times). However, duringactive delivery of stimulation to the first lateral side, IMD 14delivers a pulse train 95A including more pulses compared to duringactive delivery of stimulation to the second lateral side. Pulse train95A includes four pulses whereas pulse train 95B includes three pulses.The number of pulses in pulse trains 95A, 95B shown in FIG. 9C (as wellas the other figures) is only one example. Pulse trains 95A, 95B mayhave any suitable size in other examples.

As shown in FIG. 9C, after IMD 14 delivers second pulse train 95B to thesecond lateral side of patient 12, IMD 14 may stop delivery ofstimulation to the second lateral side and initiate delivery of pulsetrain 95A to the first lateral side of patient for a third stimulationperiod 96C. Stimulation period 96C may have the same duration asstimulation periods 96A, 96B in some examples. In addition, stimulationperiods 96A, 969, 96C do not overlap in the example of the firststimulation therapy shown in FIG. 9C.

In other examples, a combination of the regimes shown in FIGS. 9A-9C canbe used to deliver an imbalanced bilateral stimulation therapy topatient 12 when IMD 14 delivers the first stimulation therapy to patient12. Moreover, other types of stimulation regimes that include deliveringstimulation to the first and second lateral sides of patient 12 atdifferent times may be used.

FIGS. 10A-10F are schematic illustrations of stimulation signalsdelivered to the first and second lateral sides of patient 12 during thesecond electrical stimulation therapy. As shown in FIGS. 10A-10F, whenstimulation generator 42 of IMD 14 delivers stimulation signals to thefirst and second lateral sides of patient 12 at different times, thestimulation signals at least partially overlap in time. The at leastpartial overlap can be, for example, a substantially completely overlapin time (FIGS. 10A and 10B) or partial overlap in time (FIGS. 10C-10F).

FIG. 10A illustrates a stimulation pulse regime in which IMD 14 deliversthe second stimulation therapy to patient 12 by substantiallysimultaneously delivering stimulation pulses 100 to the first and secondlateral sides of patient 12 (e.g., a time overlapping manner).Stimulation pulse train 98 including a plurality of stimulation pulses100 is delivered to the first lateral side of patient 12 and pulse train99 including a plurality of stimulation pulses 100 is delivered to thesecond lateral side of patient 12. In the example shown in FIG. 10A, thepulse trains 98, 99 delivered by IMD 14 to the first and second lateralsides of patient 12, respectively, completely overlap, such that IMD 14delivers pulse trains 98, 99 to patient 12 during substantiallyoverlapping stimulation periods. Rather than stopping therapy to onelateral side of patient 12, as described with respect to FIG. 9A, IMD 14simultaneously delivers stimulation to both lateral sides of patient 12in the example shown in FIG. 10A. In addition, in the example pulseregime shown in FIG. 10A, each stimulation pulse 100 has substantiallythe same pulse width and amplitude, such that the first and secondlateral sides of patient 12 receive substantially similar intensities ofstimulation. In this way, FIG. 10A illustrates a substantially balancedbilateral stimulation therapy in which the first and second lateralsides of patient 12 receive stimulation signals during substantiallyoverlapping (e.g., completely overlapping) time slots.

FIG. 10B illustrates an example of an imbalanced second stimulationtherapy in which the first and second lateral sides of patient 12receive different stimulation pulses 102, 104 at substantially the sametime (e.g., during substantially overlapping stimulation periods). Inparticular, in the example shown in FIG. 10B, IMD 14 substantiallysimultaneously delivers a first pulse train 101 including a plurality ofstimulation pulses 102 to a first lateral side of patient 12 anddelivers a second pulse train 103 including a plurality of stimulationpulses 104 to a second lateral side of patient 12. Stimulation pulses102, 104 have substantially similar pulse widths, but have differentamplitudes. In this way, the first and second lateral sides of patient12 receive different intensities of stimulation, such that the bilateralstimulation therapy shown in FIG. 10B is imbalanced. The pulses 102, 104having substantially similar pulse widths substantially overlap in time,such that in the example shown in FIG. 10B, IMD 14 delivers stimulationto the first and second lateral sides of patient 12 in phase. In theexample shown in FIG. 10B, the pulse trains 101, 103 delivered by IMD 14to the first and second lateral sides of patient 12 substantiallyoverlap.

FIG. 10C illustrates another example of an imbalanced second stimulationtherapy in which the pulse trains 105A, 105B delivered to the first andsecond lateral sides of patient 12 include different stimulation pulses106, 108, respectively. Pulse trains 105A, 105B are delivered to patient12 in an overlapping manner such that IMD 14 delivers substantiallysimultaneous bilateral stimulation to patient 12, and such that thepulses 106, 108 within the pulse trains 105A, 105B, respectively,partially overlap in time. Pulses 106, 108 have substantially similaramplitudes, but pulses 108 have approximately half of the pulse width aspulses 106 in the example shown in FIG. 10C. As a result, although IMD14 may deliver pulse train 105A including stimulation pulses 106 to afirst lateral side of patient 12 and deliver pulse train 105B includingstimulation pulses 108 to a second lateral side of patient 12 in anoverlapping manner (such that there is substantially simultaneousbilateral stimulation), the stimulation pulses 106, 108 delivered to thefirst and second lateral sides of patient 12 only partially overlaps intime. Thus, substantially simultaneous bilateral stimulation may bedelivered to patient 12 despite a mismatch in time of stimulation pulses106, 108.

In addition, in the example shown in FIG. 10C, IMD 14 delivers pulsetrain 105A to a first lateral side of patient 12 during firststimulation period 107A and delivers pulse train 105B to a secondlateral side of patient 12 during second stimulation period 107B, wheresecond stimulation period 107B is shorter than first stimulation period107A. However, stimulation periods 107A, 107B partially overlap, suchthat IMD 14 delivers substantially simultaneous bilateral stimulation topatient 12 during at least the overlapping portions of stimulationperiods 107A, 107B. After stimulation period 107A, IMD 14 stops deliveryof stimulation therapy to the first lateral side of patient 12. Inaddition, after stimulation period 107B, IMD 14 stops delivery of thestimulation therapy to the second lateral side of patient 12. Theexample stimulation period 107A, 107B durations and pulse train 105A,105B lengths shown in FIG. 10C are only one example. In other examples,stimulation periods 107A, 107B may have any suitable duration and pulsetrains 105A, 105B may have any suitable lengths (e.g., any suitablenumber of pulses).

In some examples, pulses 106 may each have a pulse width of about 100 μsand pulses 108 may each have a pulse width of about 50 μs, and the timebetween subsequently delivered pulses 106 (T₁₀₆) may be about 50 μs toabout 100 μs. Other examples of substantially simultaneous stimulationwith mismatching pulses may also be used in accordance with thetechniques herein. For example, although pulses 108 have approximatelyhalf the pulse width of pulses 106 in the example shown in FIG. 10C, inother examples, pulses 106, 108 may have any percentage of the width aseach other, as long as IMD 14 delivers pulses 106, 108 to patient 12such that they at least partially overlap in time.

FIG. 10D illustrates another example of an imbalanced second stimulationtherapy in which the first and second lateral sides of patient 12receive different stimulation pulses 106, 110, where each pulse 106partially overlaps in time with each pulse 110. In the example shown inFIG. 10D, IMD 14 delivers first pulse 108 train including pulses 106 toa first lateral side of patient 12 and second pulse train 109 includingpulses 110 to a second lateral side of patient, where first and secondpulse trains 108, 109 substantially overlap in time, such that IMD 14delivers substantially simultaneous bilateral stimulation to patient 12.Pulse train 109 includes a plurality of bursts of pulses 110 separatedin time. Pulses 110 have approximately 25% of the pulse width as each ofthe pulses 106 in the example shown in FIG. 10D, such that although IMD14 may substantially simultaneously deliver pulse train 108 includingstimulation pulses 106 to a first lateral side of patient 12 and deliverpulse train 109 including stimulation pulses 110 to a second lateralside of patient 12, the stimulation pulses delivered to the first andsecond lateral sides of patient 12 only partially overlaps in time. Inthe example shown in FIG. 10D, the stimulation period during which IMD14 delivers pulse train 108 to the first lateral side of patient 12 isthe same as the stimulation period during which IMD 14 delivers pulsetrain 110 to the second lateral side of patient 12.

FIG. 10E illustrates another example of an imbalanced second stimulationtherapy in which IMD 14 delivers identical pulse trains includingstimulation pulses 112, 114 to the first and second lateral sides,respectively, of patient 12 such that the pulse trains are out-of-phase.As a result, pulses 112, 114 are delivered to the lateral sides ofpatient 12 at different times. In particular, IMD 14 delivers the pulsetrain to a first lateral side of patient 12 and to the second lateralside of patient 12 such that when IMD 14 delivers stimulation pulse 112to the first lateral side of patient 12, IMD 14 delivers stimulationpulse 114 to the second lateral side of patient 12, such thatstimulation pulses 112, 114 at least partially overlap in time. Inaddition, when IMD 14 delivers stimulation pulse 114 to the firstlateral side of patient 12, IMD 14 delivers stimulation pulse 112 to thesecond lateral side of patient 12, such that stimulation pulses 112, 114at least partially overlap in time. Because the pulse trains overlap,patient 12 receives substantially simultaneous bilateral stimulationthat is imbalanced.

FIG. 10F illustrates an example of balanced second stimulation therapyin which IMD 14 delivers identical pulse trains 98, 99 includingstimulation pulses 100 to patient 12 out of phase, such that pulses 100are delivered to patient 12 at different times. Pulse trains 98, 99shown in FIG. 10F are the same as the pulse trains shown in FIG. 10A. InFIG. 10A, IMD 14 delivers pulse trains 98, 99 to the respective lateralsides of patient 12 such that pulses 100 are in phase and completelyoverlap. In contrast, in FIG. 10F, IMD 14 delivers pulse trains 98, 99such that pulses 100 are out of phase and do not overlap. As a result,there is a pulse mismatch between pulses 100 of the pulse traindelivered to the first lateral side of patient 12 and pulses 100 of thepulse train delivered to the second lateral side of patient 12. Asdiscussed in further detail below with respect to FIGS. 15A and 15B,experimental results indicate that, in some cases, a substantially equalefficacy may be achieved by the stimulation regime shown in FIG. 10A(pulse match) and the stimulation regime shown in FIG. 10F (pulsemismatch).

IMD 14 may deliver pulse trains 98, 99 such that pulses 100 are out ofphase using any suitable technique. In the example shown in FIG. 10F,IMD 14 starts the delivery of pulse train 98 to the first lateral sideof patient 12 after the start of delivery of pulse train 99 to patient12. The delay may be, for example, equal to the pulse width of a pulse100 of pulse train 98. In other examples, IMD 14 may initiate deliveryof pulse trains 98, 99 to patient 12 at the same time, and pulse train98 may be configured such that no pulse 100 is immediately deliveredupon the beginning of the stimulation period in which IMD 14 activelydelivers stimulation to the first lateral side of patient 12, and pulsetrain 99 may be configured such that a pulse 100 is immediatelydelivered upon the beginning of the stimulation period in which IMD 14actively delivers stimulation to the second lateral side of patient 12.

In other examples, a combination of the regimes shown in FIGS. 10B-10Fcan be used to deliver an imbalanced bilateral stimulation therapy topatient 12 when IMD 14 delivers the second stimulation therapy topatient 12. Moreover, other types of stimulation regimes that includedelivering stimulation to the first and second lateral sides of patient12 substantially simultaneously may be used.

FIGS. 11-15B are graphs that illustrate a change in bladder contractionfrequency in response to electrical stimulation. The data illustrated inFIGS. 11-15B was obtained from a plurality of tests performed onanesthetized female laboratory rats weighing approximately 200 grams toabout 300 grams. During the tests, the body temperatures of the subjectswere maintained at approximately 37° C. and bladder contractions of oneor more test subjects were observed during an approximately 40 minuteperiod (e.g., −15 minutes to 25 minutes shown along the time axis inFIGS. 11-13). During the observation period, there was an approximately15 minute control period, followed by a 10 minute stimulation period(which is indicated by stimulation period 116 in each of FIGS. 11-13,14A, and 15A), and a 20 minute post-stimulation period. During thestimulation period, electrical stimulation was delivered to an L6 spinalnerve of each subject for about ten minutes. An exposed portion of wireelectrode (a Teflon-coated, 40-gauge, stainless steel wire availablefrom Cooner Wire, Inc. of Chatsworth, Calif.) was placed under the L6spinal nerve unilaterally or bilaterally. The electrode was connected toa S88 pulse stimulator (available from Grass Technologies of WestWarwick, Rhode Island) through a stimulation isolation unit, whichgenerated biphasic stimulation pulses having pulse widths of about 0.1ms and a frequency of about 10 Hz. A needle electrode served as theground.

A cannula was placed into the bladder of each subject via the urethraand the urethra was ligated to ensure an isovolumetric bladder. Toinduce bladder rhythmic contractions in the subject, saline was infusedinto the bladder of the subject via the cannula at a rate of about 50microliters (μL) per minute to induce a micturition reflex, which wasdefined in these experiments to be a bladder contraction of a magnitudegreater than about 10 millimeters of mercury (mmHg). Thereafter, theinfusion rate was reduced to about 10 μL a minute and continued untilabout three to about five consecutive contractions were established.After that time, the bladder rhythmic contractions continued until thesaline infusion was terminated. The control period for determining thebladder contraction frequency control value was about 15 minutes. Thebladder contractions were recorded using a pressure transducer connectedto the cannula placed in the bladder of the subject. The pressuretransducer input into an ADInstrument data acquisition system, which iscommercially available from ADInstruments of Colorado Springs, Colo.

For each test run (i.e., each 40 minute observation), a frequency ofbladder contractions was determined at approximately 5 minute intervals.The determined frequencies of bladder contractions were then normalized(i.e., divided by) by a frequency of bladder contractions of the testsubject at the time indicated by “−5 minutes” in the figures. Thenormalized bladder contraction frequencies are graphed in FIGS. 11-13,14A, and 15A. The graphs illustrated in FIGS. 11-13, 14A, and 15A eachplots frequency versus time. Frequency (normalized %) indicates afrequency of bladder contraction relative to the frequency of bladdercontractions of the test subject at time −5 minutes. Frequency(normalized %) ranges from 0% to 120%. The results of the experimentsshown in FIGS. 11-15B were analyzed with GraphPad Prism 4 software(available from GraphPad Software, Inc. of San Diego, Calif.).

For each of the subjects in the experiments conducted to generate thedata shown in FIGS. 11-15B, the threshold intensity level was determinedby determining the lowest current level at which the first visuallydiscernable muscle contraction was evoked.

The type of stimulation delivered to the test subject is indicated bythe shape of the data point illustrated in FIGS. 11-13. Each of the datapoints (i.e., open circles, solid circles, triangular data points thatinclude a single vertex at the top, and inverted triangular data pointsthat include two vertices at the top) shown in FIGS. 11-13 include anamount of variation. The variation bars, e.g., illustrated in oneexample as variation bar 118 in FIG. 11, are included to show variationsamong measurements.

The open circle data points in FIGS. 11-13 indicate measurement ofbladder contraction frequency in subjects that did not receiveelectrical stimulation (the control group). Accordingly, the open circledata points represent a bladder contraction frequency at approximately100% normalized frequency. The solid circle data points in FIGS. 11-13indicate measurement of bladder contraction frequency in subjects thatreceived unilateral electrical stimulation, which consisted ofelectrical stimulation at a target tissue site proximate a pelvic floornerve on only one lateral side of the subject's body. The unilateralstimulation was delivered at a threshold intensity level, which variedby subject and tissue site. The mean threshold intensity level for thesubjects used for the unilateral stimulation therapy was characterizedby a current amplitude of about 0.2 mA (with a variation of about 0.07mA), a frequency of about 10 Hz, and a pulse width of about 100 μs.

The triangular data points that include a single vertex at the top(e.g., pointing in a direction furthest from the x-axis) indicate themeasurement of bladder contraction frequency in subjects that receivedthe second stimulation therapy, whereby stimulation was deliveredsubstantially simultaneously to one lateral side of the subject at athreshold intensity level, which varied by subject, and to the otherlateral side of the subject at a stimulation intensity below thethreshold intensity level. The mean threshold intensity level for thesubjects used for the second stimulation therapy was characterized by acurrent amplitude of about 0.10 mA (with a variation of about 0.02 mA),a frequency of about 10 Hz, and a pulse width of about 100 μs.

The inverted triangle data points (shown in FIG. 11) that include twovertices at the top indicate the measurement of bladder contractionfrequency in subjects that received the first stimulation therapy,whereby stimulation was delivered to the two lateral sides of thesubject at alternating times. The stimulation was delivered at athreshold intensity level, which varied by subject. The mean thresholdintensity level for the subjects used for the first stimulation therapywas characterized by a current amplitude of about 0.10 mA (with avariation of about 0 mA a frequency of about 10 Hz, and a pulse width ofabout 100 μs.

In FIG. 11, the solid circle data points indicate a bladder contractionfrequency of the subjects decreased during stimulation period 116 inresponse to the delivery of the unilateral stimulation, but thengradually increased in the time period following stimulation period 116,when no stimulation was being delivered to the subjects (e.g., afterabout 5 minutes in the time course shown in FIG. 11). Thus, it wasobserved that the unilateral stimulation therapy reduced bladdercontraction frequency as the stimulation was being delivered to thesubject, but upon cessation of the unilateral stimulation therapy, thebladder contraction frequency began to increase and recovers toward thecontrol frequency, i.e., toward the bladder contraction frequencyobserved when no stimulation therapy is delivered. The solid circle datapoints indicate that reduction in bladder contraction frequency is notpronounced, but may be present, during stimulation period 116.Accordingly, the test results indicate that unilateral stimulationtherapy may reduce bladder contraction frequency by a moderate amountwhile the stimulation is being delivered to the subject.

In FIG. 11, the trajectory of the inverted triangle data points (withthe two vertices at the top) over time indicates that the bladdercontraction frequency of the subjects decreased in response to thedelivery of the first electrical stimulation therapy, which in the testsincluded delivery of stimulation to the lateral sides of the subject inan alternating fashion. The trajectory of the inverted triangle datapoints also indicate that the bladder contraction frequency of thesubjects increased towards the control bladder contraction frequency inthe post-stimulation period immediately following stimulation period116. In particular, the bladder contraction frequency decreased fromabout 100% of the control to about 60% to about 70% of the controlduring stimulation period 116, and increased to between then to betweenabout 80% to about 100% about 5 minutes after stimulation period 116.The reduction in bladder contraction frequency observed duringstimulation period 116 in response to the delivery of the firststimulation therapy is of a magnitude that may provide efficaciousbladder dysfunction therapy to patient 12.

In FIG. 11, the trajectory of the triangular data points with the singlevertex at the top over time indicates that the bladder contractionfrequency of the subjects decreased in response to the delivery of thesecond electrical stimulation therapy, which included substantiallysimultaneous imbalanced bilateral stimulation, even during the timeperiod following stimulation period 116. In particular, the bladdercontraction frequency decreased from about 100% of the control to about80% during stimulation period 116, and then to between about 60% toabout 80% about 5 minutes after stimulation period 116, and then toabout 40% to about 60% about 10 minutes after stimulation period 116.About 10 minutes after the cessation of the second stimulation therapy,the bladder contraction frequency of the subjects began to graduallyincrease towards the control frequency, but remained significantly belowthe control frequency even 20 minutes after stimulation period 116. Thereduction in bladder contraction frequency observed during bothstimulation period 116 and the post stimulation period in response tothe delivery of the first bilateral stimulation therapy is of amagnitude that may provide efficacious bladder dysfunction therapy topatient 12.

The test results shown in FIG. 11 indicate that the delivery ofbilateral stimulation therapy, whether delivered to the two lateralsides of the subject substantially simultaneously or at different times,elicited a stronger inhibitory physiological response from the subjects,and, in particular, a stronger inhibition of bladder contractions, thanthe unilateral stimulation (associated with the solid circle datapoints) alone.

The test results shown in FIG. 11 also indicate that the delivery of thesecond stimulation therapy that included substantially simultaneousbilateral stimulation therapy elicited a delayed inhibition of bladdercontractions relative to the first stimulation therapy. Moreover, theinhibition of bladder contractions appeared to be more pronounced withthe substantially simultaneous bilateral stimulation therapy compared tothe alternating bilateral stimulation therapy, e.g., based on thecomparison of the lowest frequency indicated by the data points with asingle vertex at the top to the lowest frequency indicated by theinverted triangular data points (with two vertices at the top).

The test results shown in FIG. 12 indicate that bilateral stimulationgenerated a stronger inhibitory physiological effect in the subjectscompared to the unilateral stimulation at a stimulation amplitude ofabout 0.6 mA and a frequency of about 0.5 Hz and delivered for about 10minutes. While the test results in FIG. 12 only illustrate the testresults from the second stimulation therapy (including substantiallysimultaneous bilateral stimulation), the test results shown in FIG. 11indicate that bilateral stimulation that includes delivery ofstimulation to the lateral sides of the subject in an alternatingfashion, also elicited a stronger inhibitory physiological effect in thesubjects compared to the unilateral stimulation.

In FIG. 12, the unilateral stimulation elicited a bladder contractionfrequency that was about 40% to about 50% of the control bladdercontraction frequency at the time the stimulation was delivered (atabout the beginning of stimulation period 116), but during stimulationperiod 116, the bladder contraction frequency began to increase fromthat bladder contraction frequency towards the control. At cessation ofthe unilateral stimulation therapy, the bladder contraction frequencyincreased to about 60% to about 80% of the control, and about 15 minutesafter the unilateral stimulation was delivered to patient 12 (i.e., atabout the 20 minute mark in FIG. 12), the bladder contraction frequencyof the subjects increased to greater than or equal to the controlfrequency.

In contrast, in the test results shown in FIG. 12, the bilateralstimulation elicited a elicited a bladder contraction frequency that wasabout 20% of the control bladder contraction frequency duringstimulation period 116. In addition, while the bladder contractionfrequency increased in the post-stimulation period, the bladdercontraction frequency remained below the control, as well as below thebladder contraction frequency in the post-stimulation period elicited bythe unilateral stimulation.

In the tests conducted to generate the test results shown in FIG. 13,the unilateral electrical stimulation (delivered at a stimulationamplitude of about 0.6 mA and a frequency of about 0.5 Hz and deliveredfor about 10 minutes) and bilateral electrical stimulation elicitedsubstantially similar results during stimulation period 116.

Based on at least the test results shown FIGS. 11-13, it is believedthat the unilateral stimulation therapy, substantially simultaneousbilateral stimulation therapy, and the bilateral stimulation therapythat included delivery of stimulation to the lateral sides of thesubject at different times can each generate different inhibitoryphysiological responses from a patient. The test results furtherindicate that the substantially simultaneous bilateral stimulationtherapy may elicit a greater decrease in bladder contraction frequencycompared to the unilateral stimulation therapy and the alternatingbilateral stimulation therapy. Moreover, the test results shown in FIG.11 indicate that substantially simultaneous bilateral stimulationtherapy generated a stronger inhibitory physiological response from thesubjects compared to the alternating bilateral stimulation therapy, suchthat the substantially simultaneous bilateral stimulation therapy may beuseful as a supplementary therapy (in combination with the alternatingbilateral stimulation therapy) that is delivered to patient 12 when astronger therapeutic effect is desirable.

FIGS. 14A and 14B are graphs that illustrate example time courses ofresponses of bladder contractions to unilateral stimulation, alternatingbilateral stimulation for approximately 10 minutes, alternatingbilateral stimulation for approximately 20 minutes, and substantiallysimultaneous bilateral stimulation. As with FIGS. 11-13, the dataillustrated in FIGS. 14A and 14B was obtained from a plurality of testsperformed on laboratory rats. During the tests, bladder contractions ofone or more test subjects were observed during an approximately 40minute period (i.e., a pre-stimulation period, a 10 minute stimulationperiod 116, and then a post-stimulation period, which are shown alongthe time axis in FIG. 14A). During this observation period, electricalstimulation was delivered to an L6 spinal nerve of each subject forabout ten minutes, which is indicated by stimulation period 116 in FIG.14A. For each test run (i.e., each 40 minute observation), a frequencyof bladder contractions was determined at approximately 5 minuteintervals. The determined frequencies of bladder contractions were thennormalized (i.e., divided by) by a frequency of bladder contractions ofthe test subject at the time indicated by “−5 minutes” in the figures.The normalized bladder contraction frequencies are graphed in FIG. 14A.The graphs illustrated in FIG. 14A each plots frequency versus time.Frequency (normalized %) indicates a frequency of bladder contractionrelative to the frequency of bladder contractions of the test subject attime −5 minutes. Frequency (normalized %) ranges from 0% to 120%.

The type of stimulation delivered to the test subject is indicated bythe shape of the data point illustrated in FIG. 14A. As with FIGS.11-13, each of the data points shown in FIG. 14A include an amount ofvariation, which is illustrated by a respective variation bar. The opencircle data points in FIG. 14A indicate the mean normalized bladdercontraction frequencies of 21 subjects that did not receive electricalstimulation (the control group), such that the open circle data pointsrepresent a bladder contraction frequency at approximately 100%normalized frequency. The diamond shaped data points in FIG. 14Aindicate the mean normalized bladder contraction frequencies of 15subjects that received unilateral electrical stimulation, whichconsisted of electrical stimulation at a target tissue site proximate aL6 spinal on only one lateral side of the subject's body. The unilateralstimulation was delivered to the one side of each subject at a thresholdintensity level for approximately ten minutes, where the thresholdintensity level varied by subject and tissue site. The mean thresholdintensity level for the subjects used for the unilateral stimulationtherapy was characterized by a current amplitude of about 0.15 mA (witha variation of about 0.03 mA), a frequency of about 10 Hz, and a pulsewidth of about 100 μs.

The inverted triangular data points, which include two vertices at thetop, indicate the mean normalized bladder contraction frequencies of 7subjects that received the first stimulation therapy for approximately10 minutes, whereby stimulation was delivered in an alternating mannerto the two lateral sides of the subject at the subject at a thresholdintensity level, which varied by subject. For each subject, thestimulation was first delivered to a first lateral side of the subjectfor approximately 5 minutes, followed by stimulation delivery to thesecond lateral side of the subject for approximately 5 minutes.Stimulation was stopped after stimulation delivery to the second lateralside. The mean threshold intensity level for the subjects used for thefirst stimulation therapy was characterized by about 0.14 mA (with avariation of about 0.04 mA), a frequency of about 10 Hz, and a pulsewidth of about 100 μs.

The triangular data points that include a single vertex at the top(e.g., pointing in a direction furthest from the x-axis) indicate themean normalized bladder contraction frequencies of 11 subjects thatreceived the first stimulation therapy for approximately 20 minutes,whereby, for each subject, stimulation was delivered in an alternatingmatter to the lateral sides of the subject at a threshold intensitylevel, which varied by subject. The stimulation was first delivered to afirst lateral side of the subject for approximately 5 minutes, followedby stimulation delivery to the second lateral side of the subject forapproximately 5 minutes, followed by stimulation delivery to the firstlateral side of the subject for approximately 5 minutes, followed bystimulation delivery to the second lateral side of the subject forapproximately 5 minutes. Stimulation was stopped after the second courseof stimulation delivery to the second lateral side. The mean thresholdintensity level for the subjects used for the second stimulation therapywas characterized by a current amplitude of about 0.04 mA (with avariation of about 0.01 mA), a frequency of about 10 Hz, and a pulsewidth of about 100 μs.

In order to show the results of the alternating bilateral stimulationtherapy for approximately 20 minutes and compare it to the results ofthe unilateral stimulation for approximately 10 minutes and thealternating bilateral stimulation for approximately 10 minutes, theapproximately 20 minute stimulation period was scaled to fit into the 10minute stimulation period 116 shown in FIG. 14A. As a result, thetriangular data point shown at time “stimulation 5” in FIG. 14Acorresponds to the mean bladder contraction frequency value afterstimulation was delivered to the first lateral side of the subject forapproximately 5 minutes and subsequently delivered to the second lateralside of the subject for approximately 5 minutes, and the triangular datapoint shown at time “stimulation 10” in FIG. 14A corresponds to the meanbladder contraction frequency value after stimulation was subsequentlydelivered to the first lateral side of the subject for approximately 5minutes and then to the second lateral side of the subject forapproximately 5 minutes.

In FIG. 14A, the solid circle data points indicate the mean normalizedbladder contraction frequencies of 10 subjects that received the secondstimulation therapy, which was imbalanced substantially simultaneousbilateral stimulation therapy. In these examples, for each subject,stimulation was delivered substantially simultaneously to a firstlateral side of the subject at a threshold intensity level, which variedby subject, and to the other lateral side of the subject at astimulation intensity below the threshold intensity level. The meanthreshold intensity level for the subjects used for the secondstimulation therapy was characterized by a current amplitude of about0.06 mA (with a variation of about 0.03 mA), a frequency of about 10 Hz,and a pulse width of about 100 μs.

The data shown in FIG. 14A indicates that a bladder contractionfrequency of the subjects decreased during the stimulation period 116 inresponse to the unilateral stimulation (diamond data points),alternating bilateral stimulation for approximately 10 minutes (invertedtriangular data points), alternating bilateral stimulation forapproximately 20 minutes (triangular data points), and imbalancedsubstantially simultaneous bilateral stimulation (solid circle datapoints). However, the decrease in bladder contraction frequency duringstimulation period 116 was most pronounced for the substantiallysimultaneous bilateral stimulation compared to the unilateralstimulation, alternating bilateral stimulation for approximately 10minutes, or alternating bilateral stimulation for approximately 20minutes. The data further indicates that the bladder contractionfrequency of the subjects decreased more during stimulation period 116in response to the alternating bilateral stimulation for approximately20 minutes compared to the unilateral or alternating bilateralstimulation for approximately 10 minutes, and that the bladdercontraction frequency of the subjects decreased more during stimulationperiod 116 in response to the alternating bilateral stimulation forapproximately 10 minutes compared to the unilateral stimulation.

In addition, the data shown in FIG. 14A indicates that the bladdercontraction frequency of the subjects remained relatively low comparedto the control (open circle data points) for the unilateral stimulation(diamond data points), alternating bilateral stimulation thrapproximately 10 minutes (inverted triangular data points), andalternating bilateral stimulation for approximately 20 minutes(triangular data points) both during stimulation period 116 and afterstimulation period 116. However, with the unilateral, alternatingbilateral stimulation for approximately 10 minutes, alternatingbilateral stimulation for approximately 20 minutes, and substantiallysimultaneous bilateral stimulation, the bladder contraction frequency ofthe subjects increased toward the bladder contraction frequency observedwhen no stimulation therapy was delivered in the time period immediatelyfollowing stimulation period 116. As shown in FIG. 14A, the alternatingbilateral stimulation for approximately 20 minutes appeared to result ina greater increase in bladder contraction frequency during the timeperiod immediately following stimulation period 116 compared to thealternating bilateral stimulation for approximately 10 minutes. This mayindicate, for example, the alternating bilateral stimulation forapproximately 10 minutes may have longer lasting affects compared to thealternating bilateral stimulation for approximately 20 minutes.

In FIG. 14A, the trajectory of the diamond data points over timeindicates that the bladder contraction frequency of the subjectsdecreased in response to the delivery of the unilateral stimulation. Thetrajectory of the diamond data points indicate that the bladdercontraction frequency of the subjects decreased from about 100% of thecontrol to about 75% to about 80% of the control during stimulationperiod 116, and then increased to between about 100% of the controlabout 5 minutes immediately after stimulation period 116. Duringstimulation period 116, the mean reduction in bladder contractionfrequency in response to the unilateral stimulation was about 82.04%±7%(p>0.05) of the control. The control was about 98.52%±5%.

The trajectory of the inverted triangular data points, which correspondto the alternating bilateral stimulation therapy for approximately 10minutes, over time indicate that, in response to the alternatingbilateral stimulation, the bladder contraction frequency of the subjectsdecreased from about 100% of the control to about 65% to about 70% ofthe control during stimulation period 116, and, during stimulationperiod 116, began increasing, such that after about 5 minutes afterabout 5 minutes of stimulation (5 minutes into stimulation period 116),the bladder contraction frequency of the subjects between about 75% toabout 80% of the control. During stimulation period 116, the meanreduction in bladder contraction frequency in response to thealternating bilateral stimulation therapy for approximately 10 minuteswas about 61.85%±18% (p>0.05) of the control. The reduction in bladdercontraction frequency observed during stimulation period 116 in responseto the delivery of the alternating bilateral stimulation forapproximately 10 minutes is of a magnitude that may provide efficaciousbladder dysfunction therapy to patient 12.

Also shown in FIG. 14A is a trajectory of the triangular data points,which correspond to the alternating bilateral stimulation therapy forapproximately 20 minutes. The trajectory of the triangular data pointsover time indicate that, in response to the alternating bilateralstimulation for approximately 20 minutes, the bladder contractionfrequency of the subjects decreased from about 100% of the control toabout 60% to about 65% of the control during stimulation period 116, andincreased to between then to between about 90% to about 100% of thecontrol about 5 minutes after stimulation period 116. During stimulationperiod 116, the mean reduction in bladder contraction frequency inresponse to the alternating bilateral stimulation therapy forapproximately 20 minutes was about 64.90%±16% (p>0.05) of the control.The reduction in bladder contraction frequency observed duringstimulation period 116 in response to the delivery of the alternatingbilateral stimulation for approximately 20 minutes is of a magnitudethat may provide efficacious bladder dysfunction therapy to patient 12.

Despite the increase in bladder contraction frequency after stimulationperiod 116 for both durations of the alternating bilateral stimulationtherapies, the experimental results shown in FIG. 14A indicate that bothalternating bilateral stimulation for approximately 10 minutes andalternating bilateral stimulation for approximately 20 minutes mayreduce bladder contraction frequency by a moderate amount while thestimulation is being delivered to the subject, where the moderate amountmay still be useful for managing the bladder dysfunction of the patient.

In FIG. 14A, trajectory of the solid circle data points over timeindicates that the bladder indicates that the bladder contractionfrequency of the subjects decreased in response to the delivery of thesecond electrical stimulation therapy, which was substantiallysimultaneous bilateral stimulation therapy in the experiment describedwith respect to FIG. 14A. The trajectory of the solid circle pointsindicate that the bladder contraction frequency of the subjectsdecreased from about 100% of the control to about 25% to about 30% ofthe control during stimulation period 116, and increased to between thento between about 40% to about 45% of the control about 5 minutes afterstimulation period 116. During stimulation period 116, the meanreduction in bladder contraction frequency in response to thesubstantially simultaneous bilateral stimulation therapy forapproximately 10 minutes was about 26.3%±14% (p<0.05) of the control.The reduction in bladder contraction frequency observed duringstimulation period 116 in response to the delivery of the alternatingbilateral stimulation for approximately 10 minutes and for a period oftime (e.g., about 10-20 minutes) immediately after stimulation period116 is of a magnitude that may provide efficacious bladder dysfunctiontherapy to patient 12.

The experimental results shown in FIG. 14A indicate that the delivery ofbilateral stimulation therapy, whether delivered to the two lateralsides of the subject substantially simultaneously or at different times,elicited a stronger inhibitory physiological response from the subjects,and, in particular, a stronger inhibition of bladder contractions, thanthe unilateral stimulation (associated with the solid circle datapoints) alone. In addition, the experimental results shown in FIG. 14Aindicate that the delivery of substantially simultaneous bilateralstimulation therapy elicited a stronger inhibitory physiologicalresponse from the subjects, and, in particular, a stronger inhibition ofbladder contractions, during stimulation period 116 than the bilateralstimulation delivered to the lateral sides of the subject at differenttimes.

FIG. 14B is a bar graph that illustrates the mean response of thesubjects during stimulation period 116 for each of the types ofstimulation described with respect to FIG. 14A, FIG. 14B furtherillustrates that the alternating bilateral stimulation for approximately10 minutes and alternating bilateral stimulation therapy forapproximately 20 minutes each elicited a relatively moderate reductionin bladder contraction frequency during stimulation period 116 comparedto the substantially simultaneous bilateral stimulation. In particular,in response to the alternating bilateral stimulation for approximately20 minutes, the mean response of the subjects during stimulation period116 was a bladder contraction frequency was about 65% of the controland, in response to the alternating bilateral stimulation forapproximately 10 minutes, the mean response of the subjects duringstimulation period 116 was a bladder contraction frequency was about 61%of the control. The mean response of the subjects during stimulationperiod 116 to the second type of stimulation therapy, i.e.,substantially simultaneous bilateral stimulation therapy in theexperiments conducted to generate the data shown in FIG. 14B, was abladder contraction frequency that was about 20% of the control.

As discussed above, during substantially simultaneous bilateralstimulation therapy, the electrical stimulation signal trains deliveredto the lateral sides of patient 12 overlap, such that there is anoverlap in stimulation periods for the stimulation delivered to eachlateral side of patient 12. Within each signal train, however, thestimulation signals may be delivered at different times or at the sametime. For example, as discussed with respect to FIG. 10F, the pulseswithin the pulse trains may be mismatched such that pulses may not bedelivered to the two lateral sides of patient 12 substantiallysimultaneously. FIGS. 15A and 15B are graphs that illustrate the affectof pulse match and pulse mismatch on bladder contraction frequencyduring delivery of substantially simultaneous bilateral stimulation.

As with FIGS. 11-14B, the data illustrated in FIGS. 15A and 15B wasobtained from a plurality of tests performed on laboratory rats. Duringthe tests, bladder contractions of one or more test subjects wereobserved during an approximately 40 minute period (i.e., apre-stimulation period, a 10 minute stimulation period 116, and then apost-stimulation period, which are shown along the time axis in FIG.15A). During this observation period, electrical stimulation wasdelivered to an L6 spinal nerve of each subject for about ten minutes,which is indicated by stimulation period 116 in FIG. 15A. For each testrun (i.e., each 40 minute observation), a frequency of bladdercontractions was determined at approximately 5 minute intervals. Thenormalized bladder contraction frequencies are graphed in FIG. 15A.

The type of stimulation delivered to the test subjects is indicated bythe shape of the data point illustrated in FIG. 15A. As with FIGS.11-13, each of the data points shown in FIG. 15A include an amount ofvariation, which is illustrated by a respective variation bar. The opencircle data points in FIG. 15A indicate the mean normalized bladdercontraction frequencies of 21 subjects that did not receive electricalstimulation (the control group), such that the open circle data pointsrepresent a bladder contraction frequency at approximately 100%normalized frequency. The diamond shaped data points in FIG. 15Aindicate the mean normalized bladder contraction frequencies of 6subjects that received substantially simultaneous bilateral stimulationat about 80% of the threshold intensity level (indicated as “0.8*Tmot”in FIGS. 15A and 15B) of the subject for approximately ten minutes,where the pulse trains were delivered to the two lateral sides of thesubject such that the pulses of the pulse trains substantially matchedin time (e.g., as shown in FIG. 10A). In this example, the electricalstimulator delivered the pulses to the lateral side of the patients witha delay of about 0.05 seconds. The threshold intensity level was a motorthreshold and varied by subject and tissue site. The mean thresholdintensity level for the subjects used for the substantially simultaneousbilateral stimulation at about 80% of the threshold intensity and with apulse match was characterized by a current amplitude of about 0.17 mA(with a variation of about 0.01 mA), a frequency of about 10 Hz, and apulse width of about 100 μs.

The square data points in FIG. 15A indicate the mean normalized bladdercontraction frequencies of 6 subjects that received substantiallysimultaneous bilateral stimulation at about 0.8 percent of the thresholdintensity level of the subject for approximately ten minutes, where thepulse trains were delivered to the two lateral sides of the subject suchthat the pulses of the pulse trains did not match in time (e.g., asshown in FIG. 10F). Again, the threshold intensity level varied bysubject and tissue site. The mean threshold intensity level for thesubjects used for the substantially simultaneous bilateral stimulationat about 80% of the threshold intensity and with a pulse mismatch wascharacterized by a current amplitude of about 0.18 mA (with a variationof about 0.02 mA), a frequency of about 10 Hz, and a pulse width ofabout 100 μs.

The inverted triangular data points, which include two vertices at thetop, indicate the mean normalized bladder contraction frequencies of 5subjects that received substantially simultaneous bilateral stimulationat about 100% of the threshold intensity level of the subject forapproximately ten minutes, where the pulse trains were delivered to thetwo lateral sides of the subject such that the pulses of the pulsetrains matched in time. The mean threshold intensity level for thesubjects used for the substantially simultaneous bilateral stimulationat about 100% percent of the threshold intensity indicated as “1*Tmot”in FIGS. 15A and 15B) and with a pulse match was characterized by acurrent amplitude of about 0.15 mA (with a variation of about 0.03 mA),a frequency of about 10 Hz, and a pulse width of about 100 μs.

The triangular data points that include a single vertex at the topindicate the mean normalized bladder contraction frequencies of 8subjects that received substantially simultaneous bilateral stimulationat about 100% of the threshold intensity level of the subject forapproximately ten minutes, where the pulse trains were delivered to thetwo lateral sides of the subject such that the pulses of the pulsetrains did not match in time. The mean threshold intensity level for thesubjects used for the substantially simultaneous bilateral stimulationat about 100% of the threshold intensity and with a pulse mismatch wascharacterized by a current amplitude of about 0.21 mA (with a variationof about 0.03 mA), a frequency of about 10 Hz, and a pulse width ofabout 100 μs.

The experimental data shown in FIG. 15A is summarized in FIG. 15B, whichis a bar graph that illustrates the mean response of the subjects duringstimulation period 116 for each of the types of stimulation describedwith respect to FIG. 15A. The data shown in FIGS. 15A and 15B indicatesthat, for substantially simultaneous bilateral stimulation in which thepulse trains delivered to both lateral sides of the subjects overlapped,the pulse match and pulse mismatch of the pulses delivered to each ofthe lateral sides of the patient within the overlapping pulse trains didnot appear to have a relatively significant impact on the reduction inbladder contraction frequency.

For example, in response to the substantially simultaneous bilateralstimulation delivered at about 80% of the threshold intensity level forthe subjects with a pulse match, the mean response of the subjectsduring stimulation period 116 was a reduction in bladder contractionfrequency of about 74.33%±14% (p>0.05) of the control and in response tothe substantially simultaneous bilateral stimulation delivered at about80% of the threshold intensity level for the subjects with a pulsemismatch, the response of the subjects during stimulation period 116 wasa reduction in bladder contraction frequency of about 71.54%±11%(p>0.05) of the control. In addition, in response to the substantiallysimultaneous bilateral stimulation delivered at about 100% of thethreshold intensity level for the subjects, the mean response of thesubjects during stimulation period 116 was a bladder contractionfrequency of about 28.24%±11% (p<0.05) of the control for the pulsematch stimulation and about 15.62%±9% (p<0.05) of the control for thepulse mismatch stimulation. The experimental results shown in FIGS. 15Aand 15B indicate that inhibition of bladder contractions may not requireprecise pulse locking on each lateral side of the patient.

FIG. 16 is a conceptual diagram of therapy system 1, which is configuredto determine an impedance of bladder 122 of patient 12. FIG. 16 alsoillustrates internal urinary sphincter 124 and external urinarysphincter 126. Therapy system 120 is similar to therapy system 10 ofFIG. 1 and includes IMD 14, which is coupled to leads 16, 18, andprogrammer 20. In the example shown in FIG. 11, electrodes 128A, 128B oflead 16 and electrodes 130A, 130B of lead 18 are positioned proximate toan exterior surface of the wall of bladder 122. In some examples,electrodes 128A, 128B, 130A, and 130B may be sutured or otherwiseaffixed to the bladder wall. In other examples, electrodes 128A, 128B,130A, and 130B may be implanted within the bladder wall. Electrodes128A, 128B may be separate from electrodes 30 (FIG. 3) or may be a partof the electrodes 30. Similarly, electrodes 130A, 130B may be separatefrom electrodes 32 or may be a part of electrodes 32. In addition, inother examples, electrodes 128A, 128B, 130A, 130B are carried by otherleads.

Processor 40 (FIG. 3) of IMD 14 may determine impedance of bladder 122using a four-wire (or Kelvin) measurement technique. In other examples,IMD 14 may measure bladder impedance using a two-wire sensingarrangement. In either case, IMD 14 may transmit an electricalmeasurement signal, such as a current, through bladder 122 via leads 16,18, and determine impedance of bladder 122 based on the transmittedelectrical signal. Such an impedance measurement may be utilized todetect a bladder contraction, determine a fullness (i.e., a bladder filllevel) of bladder 122, or the like.

In the example four-wire arrangement shown in FIG. 16, electrodes 128Aand 130A and electrodes 12813 and 130B, may be located substantiallyopposite each other relative to the center of bladder 122. For exampleelectrodes 128A and 130A may be placed on opposing sides of bladder,either anterior and posterior or left and right. To measure theimpedance of bladder 122, stimulation generator 42 (FIG. 3) of IMD 14 ora separate impedance module of IMD 14 may source an electrical signal,such as current, to electrode 18A via lead 16, while electrode 130A vialead 18 sinks the electrical signal. In some examples, for collection ofimpedance measurements, IMD 14 may deliver electrical current signalsthat do not deliver stimulation therapy to bladder 122.

Voltage measurement circuitry of IMD 14 may measure the voltage betweenelectrode 128B and electrode 12B via leads 16, 18, respectively. Thevoltage measurement circuitry 62 may include, for example, sample andhold circuitry or other suitable circuitry for measuring voltageamplitudes. Processor 40 determines the impedance of bladder 122 using aknown value of the electrical signal sourced the determined voltage.

Although the techniques are primarily described in this disclosure formanaging bladder dysfunction, the techniques may also be applied tomanage fecal urgency, fecal incontinence, pain, and other conditions. Infecal incontinence examples, an IMD delivers the substantiallysimultaneous bilateral stimulation at a stimulation intensity greaterthan or equal to the threshold stimulation intensity when patient inputis received, when a patient parameter indicative of an imminent fecalincontinence event is detected, when a patient parameter indicative ofan increased probability of an occurrence of a fecal incontinence eventis detected (e.g., an increased patient activity level), or when apredetermined period of time has passed. The patient parameter mayinclude, for example, contraction of the anal sphincter, patientactivity level or patient posture state. The IMD may use any suitablesensing mechanism to detect contraction of the anal sphincter, such as apressure sensor or an EMG sensor.

The techniques described in this disclosure, including those attributedto IMD 14, programmer 20, or various constituent components, may beimplemented, at least in part, in hardware, software, firmware or anycombination thereof. For example, various aspects of the techniques maybe implemented within one or more processors, including one or moremicroprocessors, DSPs, ASICs, FPGAs, or any other equivalent integratedor discrete logic circuitry, as well as any combinations of suchcomponents, embodied in programmers, such as physician or patientprogrammers, stimulators, image processing devices or other devices. Theterm “processor” or “processing circuitry” may generally refer to any ofthe foregoing logic circuitry, alone or in combination with other logiccircuitry, or any other equivalent circuitry.

Such hardware, software, and/or firmware may be implemented within thesame device or within separate devices to support the various operationsand functions described in this disclosure. While the techniquesdescribed herein are primarily described as being performed by processor40 of IMD 14 and/or processor 60 of programmer 14, any one or more partsof the techniques described herein may be implemented by a processor ofone of IMD 14, programmer 14, or another computing device, alone or incombination with each other.

In addition, any of the described units, modules or components may beimplemented together or separately as discrete but interoperable logicdevices. Depiction of different features as modules or units is intendedto highlight different functional aspects and does not necessarily implythat such modules or units must be realized by separate hardware orsoftware components. Rather, functionality associated with one or moremodules or units may be performed by separate hardware or softwarecomponents, or integrated within common or separate hardware or softwarecomponents.

When implemented in software, the functionality ascribed to the systems,devices and techniques described in this disclosure may be embodied asinstructions on a computer-readable medium such as RAM, ROM, NVRAM,EEPROM, FLASH memory, magnetic data storage media, optical data storagemedia, or the like. The instructions may be executed to support one ormore aspects of the functionality described in this disclosure.

Various examples have been described. These and other examples arewithin the scope of the following claims.

What is claimed is:
 1. A method comprising: with a processor,controlling a stimulation generator to deliver a first electricalstimulation therapy to a patient, wherein the first electricalstimulation therapy comprises delivery of electrical stimulation to afirst lateral side of the patient and a second lateral side of thepatient at different times; after initiating delivery of the firstelectrical stimulation therapy, detecting a trigger event; and inresponse to detecting the trigger event, with the processor, controllingthe stimulation generator to deliver a second electrical stimulationtherapy to the patient, wherein the second electrical stimulationtherapy comprises delivery of electrical stimulation substantiallysimultaneously to the first and second lateral sides of the patient. 2.The method of claim 1, wherein controlling the stimulation generator todeliver the first electrical stimulation therapy comprises controllingthe stimulation generator to alternate delivery of electricalstimulation to the first and second lateral sides of the patient.
 3. Themethod of claim 1, wherein controlling the stimulation generator todeliver at least one of the first or second electrical stimulationtherapies comprises controlling the stimulation generator to deliversubstantially balanced electrical stimulation to the first and secondlateral sides of the patient.
 4. The method of claim 3, whereincontrolling the stimulation generator to deliver the substantiallybalanced electrical stimulation to the first and second lateral sides ofthe patient comprises controlling the stimulation generator to deliverelectrical stimulation at substantially equal intensity levels to thefirst and second lateral sides of the patient.
 5. The method of claim 3,wherein controlling the stimulation generator to deliver thesubstantially balanced electrical stimulation to the first and secondlateral sides of the patient comprises controlling the stimulationgenerator to deliver electrical stimulation to the first and secondlateral sides of the patient for substantially equal durations of time.6. The method of claim 1, wherein controlling the stimulation generatorto deliver at least one of the first or second electrical stimulationtherapies comprises controlling the stimulation generator to deliverimbalanced electrical stimulation to the first and second lateral sidesof the patient.
 7. The method of claim 6, wherein controlling thestimulation generator to deliver the imbalanced electrical stimulationcomprises controlling the stimulation generator to deliver electricalstimulation to the first lateral side of the patient at a firststimulation intensity level and controlling the stimulation generator todeliver electrical stimulation to the second lateral side of the patientat a second stimulation intensity level that is different than the firststimulation intensity level.
 8. The method of claim 6, whereincontrolling the stimulation generator to deliver the substantiallyimbalanced electrical stimulation to the first and second lateral sidesof the patient comprises controlling the stimulation generator todeliver electrical stimulation to the first and second lateral sides ofthe patient for substantially different durations of time.
 9. The methodof claim 1, wherein controlling the stimulation generator to deliver atleast one of the first or second electrical stimulation therapiescomprises controlling the stimulation generator to deliver electricalstimulation to a first tissue site on the first lateral side of thepatient via electrodes positioned on the first lateral side of thepatient, and deliver electrical stimulation to a second tissue site onthe second lateral side of the patient via electrodes positioned on thesecond lateral side of the patient, wherein the first and second tissuesites are proximate to branches of a same nerve.
 10. The method of claim1, wherein controlling the stimulation generator to deliver at least oneof the first or second electrical stimulation therapies comprisescontrolling the stimulation generator to deliver electrical stimulationto a first tissue site on the first lateral side of the patient viaelectrodes positioned on the first lateral side of the patient, anddeliver electrical stimulation to a second tissue site on the secondlateral side of the patient via electrodes positioned on the secondlateral side of the patient, wherein the first and second tissue sitesare proximate to branches of different nerves.
 11. The method of claim1, wherein detecting the trigger event comprises detecting the triggerevent while the first electrical stimulation therapy is being deliveredto the patient.
 12. The method of claim 1, wherein detecting the triggerevent comprises, with the processor, detecting a bladder conditionindicative of at least one of an increased possibility of an involuntaryvoiding event or an imminent involuntary voiding event.
 13. The methodof claim 1, wherein detecting the trigger event comprises receivingpatient input via a user interface.
 14. The method of claim 1, whereindetecting the trigger event comprises, with the processor, at least oneof detecting a predetermined time of day or detecting expiration of atimer.
 15. The method of claim 14, further comprising, with theprocessor, starting the timer when the first electrical stimulationtherapy is delivered to the patient.
 16. The method of claim 1, furthercomprising: detecting a voiding event after initiating delivery of thesecond electrical stimulation therapy; and after detecting the voidingevent, controlling the stimulation generator to terminate delivery ofthe second electrical stimulation therapy and deliver the firstelectrical stimulation therapy to the patient.
 17. The method of claim1, wherein controlling the stimulation generator to deliver the secondelectrical stimulation therapy comprises controlling the stimulationgenerator to deliver the second electrical stimulation therapy forpredetermined period of time.
 18. The method of claim 17, furthercomprising: after the stimulation generator delivers the secondelectrical stimulation therapy for the predetermined period of time,determining whether the trigger event is detected again; controlling thestimulation generator to deliver the second electrical stimulationtherapy for the predetermined of time in response to detecting thetrigger event again; and controlling the stimulation generator todeliver the first electrical stimulation therapy in response to notdetecting the trigger event again.
 19. A system comprising: astimulation generator configured to generate and deliver electricalstimulation to a patient; and a processor configured to control thestimulation generator to deliver a first electrical stimulation therapyto the patient, wherein the first electrical stimulation therapycomprises delivery of electrical stimulation to a first lateral side ofthe patient and a second lateral side of the patient at different times,and wherein the processor is further configured to detect a triggerevent after initiating delivery of the first electrical stimulationtherapy and, in response to detecting the trigger event, control thestimulation generator to deliver a second electrical stimulation therapyto the patient, wherein the second electrical stimulation therapycomprises delivery of electrical stimulation substantiallysimultaneously to the first and second lateral sides of the patient. 20.The system of claim 19, wherein the processor is configured to controlthe stimulation generator to deliver the first electrical stimulationtherapy by at least alternating delivery of electrical stimulation tothe first and second lateral sides of the patient.
 21. The system ofclaim 19, wherein at least one of the first or second electricalstimulation therapies comprises delivery of substantially balancedelectrical stimulation therapy to the first and second lateral sides ofthe patient.
 22. The system of claim 21, wherein the substantiallybalanced electrical stimulation therapy comprises delivery of electricalstimulation at substantially equal intensity levels to the first andsecond lateral sides of the patient.
 23. The system of claim 21, whereinthe substantially balanced electrical stimulation therapy comprisesdelivery of electrical stimulation to the first and second lateral sidesof the patient for substantially equal durations of time.
 24. The systemof claim 19, wherein at least one of the first or second stimulationtherapies comprises delivery of imbalanced electrical stimulationtherapy to the first and second lateral sides of the patient.
 25. Thesystem of claim 24, wherein the processor controls the stimulationgenerator to deliver the imbalanced electrical stimulation therapy by atleast delivering electrical stimulation to the first lateral side of thepatient at a first stimulation intensity level and delivering electricalstimulation to the second lateral side of the patient at a secondstimulation intensity level that is different than the first stimulationintensity level.
 26. The system of claim 24, wherein the substantiallybalanced electrical stimulation therapy to the first and second lateralsides of the patient comprises delivery of electrical stimulation to thefirst and second lateral sides of the patient for substantiallydifferent durations of time.
 27. The system of claim 19, furthercomprising a first set of electrodes configured to be positioned on thefirst lateral side of the patient and a second set of electrodesconfigured to be positioned on the second lateral side of the patient,wherein the stimulation generator is configured to deliver at least oneof the first or second electrical stimulation therapies by at leastdelivering electrical stimulation to a first tissue site on the firstlateral side of the patient via the first set of electrodes anddelivering electrical stimulation to a second tissue site on the secondlateral side of the patient via the second set of electrodes.
 28. Thesystem of claim 19, further comprising a sensor configured to generate asignal indicative of a physiological parameter of the patient, whereinthe processor is configured to detect the trigger event by at leastdetecting, based on the signal, a bladder condition indicative of atleast one of an increased possibility of an involuntary voiding event oran imminent involuntary voiding event.
 29. The system of claim 19,further comprising a user interface, wherein the processor is configuredto detect the trigger event by at least receiving input via the userinterface.
 30. The system of claim 19, wherein the processor isconfigured to detect the trigger event by at least one of detecting apredetermined time of day or detecting expiration of a timer.
 31. Thesystem of claim 30, wherein the processor is configured to start thetimer when the first stimulation therapy is delivered to the patient.32. The system of claim 19, wherein the processor is configured todetect a voiding event after initiating delivery of the secondstimulation therapy, control the stimulation generator to deliver thesecond stimulation therapy until the voluntary voiding event isdetected, and, after detecting the voiding event, control thestimulation generator to terminate delivery of the second stimulationtherapy and deliver the first stimulation therapy to the patient. 33.The system of claim 19, wherein the processor is configured to controlthe stimulation generator to deliver the second stimulation therapy forpredetermined period of time.
 34. The system of claim 33, wherein theprocessor is configured to determine, after the stimulation generatordelivers the second stimulation therapy to the patient for thepredetermined period of time, whether the trigger event is detectedagain, and control the stimulation generator to deliver the secondstimulation therapy for the predetermined of time in response todetermining the trigger event is detected again and control thestimulation generator to deliver the first stimulation therapy inresponse to determining the trigger event is not detected again.
 35. Asystem comprising: means for delivering electrical stimulation therapyto a patient; means for detecting a trigger event after initiatingdelivery of the first electrical stimulation therapy; and means forcontrolling the means for delivering electrical stimulation therapy,wherein the means for controlling is configured to control the means fordelivering electrical stimulation therapy to deliver a first electricalstimulation therapy to a patient, wherein the first electricalstimulation therapy comprises delivery of electrical stimulation to afirst lateral side of the patient and a second lateral side of thepatient at different times, the means for controlling being furtherconfigured to, in response to detection of the trigger event, controlthe means for delivering electrical stimulation therapy to deliver asecond electrical stimulation therapy to the patient, wherein the secondelectrical stimulation therapy comprises delivery of electricalstimulation substantially simultaneously to the first and second lateralsides of the patient.
 36. The system of claim 35, wherein at least oneof the first or second electrical stimulation therapies comprisesdelivery of substantially balanced electrical stimulation to the firstand second lateral sides of the patient.
 37. The system of claim 35,wherein at least one of the first or second electrical stimulationtherapies comprises delivery of imbalanced electrical stimulation to thefirst and second lateral sides of the patient.
 38. The system of claim35, wherein the trigger event comprises at least one of a bladdercondition indicative of at least one of an increased possibility of aninvoluntary voiding event or an imminent involuntary voiding event,patient input, detection of a predetermined time of day, or expirationof a timer.
 39. A computer-readable medium comprising instructions that,when executed by a processor, cause the processor to: control astimulation generator to deliver a first electrical stimulation therapyto a patient, wherein the first electrical stimulation therapy comprisesdelivery of electrical stimulation to a first lateral side of thepatient and a second lateral side of the patient at different times;detect a trigger event after the first stimulation therapy is initiated;and in response to detecting the trigger event, control the stimulationgenerator to deliver a second electrical stimulation therapy to thepatient, wherein the second electrical stimulation therapy comprisesdelivery of electrical stimulation substantially simultaneously to thefirst and second lateral sides of the patient.
 40. The computer-readablemedium of claim 39, wherein at least one of the first or secondelectrical stimulation therapies comprises delivery of substantiallybalanced electrical stimulation to the first and second lateral sides ofthe patient.
 41. The computer-readable medium of claim 39, wherein atleast one of the first or second electrical stimulation therapiescomprises delivery of imbalanced electrical stimulation to the first andsecond lateral sides of the patient.
 42. The computer-readable medium ofclaim 39, wherein the trigger event comprises at least one of a bladdercondition indicative of at least one of an increased possibility of aninvoluntary voiding event or an imminent involuntary voiding event,patient input, a predetermined time of day, or expiration of a timer.